{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T20:33:16Z","timestamp":1779395596670,"version":"3.53.1"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several psychiatric, neurologic and neurodegenerative disorders present increased brain ventricles volume, being hydrocephalus the disease with the major manifestation of ventriculomegaly caused by the accumulation of high amounts of cerebrospinal fluid (CSF). The molecules and pathomechanisms underlying cerebral ventricular enlargement are widely unknown. <jats:italic>Kinase D interacting substrate of 220<\/jats:italic>\u2009<jats:italic>kDa<\/jats:italic> (<jats:italic>KIDINS220)<\/jats:italic> gene has been recently associated with schizophrenia and with a novel syndrome characterized by spastic paraplegia, intellectual disability, nystagmus and obesity (SINO syndrome), diseases frequently occurring with ventriculomegaly. Here we show that Kidins220, a transmembrane protein effector of various key neuronal signalling pathways, is a critical regulator of CSF homeostasis. We observe that both KIDINS220 and the water channel aquaporin-4 (AQP4) are markedly downregulated at the ventricular ependymal lining of idiopathic normal pressure hydrocephalus (iNPH) patients. We also find that Kidins220 deficient mice develop ventriculomegaly accompanied by water dyshomeostasis and loss of AQP4 in the brain ventricular ependymal layer and astrocytes. Kidins220 is a known cargo of the SNX27-retromer, a complex that redirects endocytosed plasma membrane proteins (cargos) back to the cell surface, thus avoiding their targeting to lysosomes for degradation. Mechanistically, we show that AQP4 is a novel cargo of the SNX27-retromer and that Kidins220 deficiency promotes a striking and unexpected downregulation of the SNX27-retromer that results in AQP4 lysosomal degradation. Accordingly, SNX27 silencing decreases AQP4 levels in wild-type astrocytes whereas SNX27 overexpression restores AQP4 content in Kidins220 deficient astrocytes. Together our data suggest that the KIDINS220-SNX27-retromer-AQP4 pathway is involved in human ventriculomegaly and open novel therapeutic perspectives.<\/jats:p>","DOI":"10.1038\/s41380-021-01127-9","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T10:04:53Z","timestamp":1621245893000},"page":"6411-6426","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation"],"prefix":"10.1038","volume":"26","author":[{"given":"Ana","family":"del Puerto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Pose-Utrilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Sim\u00f3n-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"L\u00f3pez-Men\u00e9ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio J.","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Porlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis S. M.","family":"Pajuelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Cano-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Mart\u00ed-Prado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Sebasti\u00e1n-Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina P.","family":"S\u00e1nchez-Carralero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Cesca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-8745","authenticated-orcid":false,"given":"Giampietro","family":"Schiavo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidro","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Fari\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1410-8621","authenticated-orcid":false,"given":"Miguel R.","family":"Campanero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4326-9005","authenticated-orcid":false,"given":"Teresa","family":"Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"1127_CR1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/ddrr.94","volume":"16","author":"MR Del Bigio","year":"2010","unstructured":"Del Bigio MR. Neuropathology and structural changes in hydrocephalus. Dev Disabil Res Rev. 2010;16:16\u201322.","journal-title":"Dev Disabil Res Rev"},{"key":"1127_CR2","doi-asserted-by":"publisher","first-page":"859","DOI":"10.2176\/nmc.50.859","volume":"50","author":"S Oi","year":"2010","unstructured":"Oi S. Hydrocephalus research update-controversies in definition and classification of hydrocephalus. Neurol Med Chir (Tokyo). 2010;50:859\u201369.","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"1127_CR3","doi-asserted-by":"publisher","first-page":"e28426","DOI":"10.4161\/tisb.28426","volume":"2","author":"AJ Jimenez","year":"2014","unstructured":"Jimenez AJ, Dominguez-Pinos MD, Guerra MM, Fernandez-Llebrez P, Perez-Figares JM. Structure and function of the ependymal barrier and diseases associated with ependyma disruption. Tissue Barriers. 2014;2:e28426.","journal-title":"Tissue Barriers"},{"key":"1127_CR4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/B978-0-12-802395-2.00005-5","volume":"145","author":"V Leinonen","year":"2017","unstructured":"Leinonen V, Vanninen R, Rauramaa T. Cerebrospinal fluid circulation and hydrocephalus. Handb Clin Neurol. 2017;145:39\u201350.","journal-title":"Handb Clin Neurol"},{"key":"1127_CR5","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/S0140-6736(76)90890-4","volume":"2","author":"EC Johnstone","year":"1976","unstructured":"Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet. 1976;2:924\u20136.","journal-title":"Lancet"},{"key":"1127_CR6","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.schres.2010.03.036","volume":"120","author":"MJ Kempton","year":"2010","unstructured":"Kempton MJ, Stahl D, Williams SC, DeLisi LE. Progressive lateral ventricular enlargement in schizophrenia: a meta-analysis of longitudinal MRI studies. Schizophr Res. 2010;120:54\u201362.","journal-title":"Schizophr Res"},{"key":"1127_CR7","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.neurobiolaging.2017.03.012","volume":"55","author":"E Mak","year":"2017","unstructured":"Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, et al. Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson\u2019s disease. Neurobiol Aging. 2017;55:78\u201390.","journal-title":"Neurobiol Aging"},{"key":"1127_CR8","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1093\/brain\/awn146","volume":"131","author":"SM Nestor","year":"2008","unstructured":"Nestor SM, Rupsingh R, Borrie M, Smith M, Accomazzi V, Wells JL, et al. Ventricular enlargement as a possible measure of Alzheimer\u2019s disease progression validated using the Alzheimer\u2019s disease neuroimaging initiative database. Brain. 2008;131:2443\u201354.","journal-title":"Brain"},{"key":"1127_CR9","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/S1474-4422(03)00487-3","volume":"2","author":"GD Silverberg","year":"2003","unstructured":"Silverberg GD, Mayo M, Saul T, Rubenstein E, McGuire D. Alzheimer\u2019s disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis. Lancet Neurol. 2003;2:506\u201311.","journal-title":"Lancet Neurol"},{"key":"1127_CR10","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.nrl.2016.03.010","volume":"33","author":"R Martin-Laez","year":"2018","unstructured":"Martin-Laez R, Valle-San Roman N, Rodriguez-Rodriguez EM, Marco-de Lucas E, Berciano Blanco JA, Vazquez-Barquero A. Current concepts on the pathophysiology of idiopathic chronic adult hydrocephalus: are we facing another neurodegenerative disease? Neurologia. 2018;33:449\u201358.","journal-title":"Neurologia"},{"key":"1127_CR11","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.molmed.2019.11.008","volume":"26","author":"BC Reeves","year":"2020","unstructured":"Reeves BC, Karimy JK, Kundishora AJ, Mestre H, Cerci HM, Matouk C, et al. Glymphatic system impairment in alzheimer\u2019s disease and idiopathic normal pressure hydrocephalus. Trends Mol Med. 2020;26:285\u201395.","journal-title":"Trends Mol Med"},{"key":"1127_CR12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997","volume":"17","author":"S Nielsen","year":"1997","unstructured":"Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP. Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci. 1997;17:171\u201380.","journal-title":"J Neurosci"},{"key":"1127_CR13","doi-asserted-by":"publisher","first-page":"11981","DOI":"10.1073\/pnas.95.20.11981","volume":"95","author":"JE Rash","year":"1998","unstructured":"Rash JE, Yasumura T, Hudson CS, Agre P, Nielsen S. Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. Proc Natl Acad Sci U.S.A. 1998;95:11981\u20136.","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"1127_CR14","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1002\/jnr.21927","volume":"87","author":"X Feng","year":"2009","unstructured":"Feng X, Papadopoulos MC, Liu J, Li L, Zhang D, Zhang H, et al. Sporadic obstructive hydrocephalus in Aqp4 null mice. J Neurosci Res. 2009;87:1150\u20135.","journal-title":"J Neurosci Res"},{"key":"1127_CR15","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/sj.jcbfm.9600306","volume":"26","author":"O Bloch","year":"2006","unstructured":"Bloch O, Auguste KI, Manley GT, Verkman AS. Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice. J Cereb Blood Flow Metab. 2006;26:1527\u201337.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1127_CR16","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","volume":"4","author":"JJ Iliff","year":"2012","unstructured":"Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med. 2012;4:147ra111.","journal-title":"Sci Transl Med"},{"key":"1127_CR17","doi-asserted-by":"publisher","first-page":"17815","DOI":"10.1073\/pnas.1110655108","volume":"108","author":"NN Haj-Yasein","year":"2011","unstructured":"Haj-Yasein NN, Vindedal GF, Eilert-Olsen M, Gundersen GA, Skare O, Laake P, et al. Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet. Proc Natl Acad Sci U.S.A. 2011;108:17815\u201320.","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"1127_CR18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.mcn.2016.10.004","volume":"77","author":"GF Vindedal","year":"2016","unstructured":"Vindedal GF, Thoren AE, Jensen V, Klungland A, Zhang Y, Holtzman MJ, et al. Removal of aquaporin-4 from glial and ependymal membranes causes brain water accumulation. Mol Cell Neurosci. 2016;77:47\u201352.","journal-title":"Mol Cell Neurosci"},{"key":"1127_CR19","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1152\/physrev.00011.2013","volume":"93","author":"EA Nagelhus","year":"2013","unstructured":"Nagelhus EA, Ottersen OP. Physiological roles of aquaporin-4 in brain. Physiol Rev. 2013;93:1543\u201362.","journal-title":"Physiol Rev"},{"key":"1127_CR20","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/nrn3468","volume":"14","author":"MC Papadopoulos","year":"2013","unstructured":"Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system. Nat Rev Neurosci. 2013;14:265\u201377.","journal-title":"Nat Rev Neurosci"},{"key":"1127_CR21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1177\/1073858418775027","volume":"25","author":"T Nakada","year":"2019","unstructured":"Nakada T, Kwee IL. Fluid dynamics inside the brain barrier: current concept of interstitial flow, glymphatic flow, and cerebrospinal fluid circulation in the brain. Neuroscientist. 2019;25:155\u201366.","journal-title":"Neuroscientist"},{"key":"1127_CR22","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1111\/nan.12420","volume":"44","author":"PK Eide","year":"2018","unstructured":"Eide PK, Hansson HA. Astrogliosis and impaired aquaporin-4 and dystrophin systems in idiopathic normal pressure hydrocephalus. Neuropathol Appl Neurobiol. 2018;44:474\u201390.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1127_CR23","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/glia.23528","volume":"67","author":"MM Hasan-Olive","year":"2019","unstructured":"Hasan-Olive MM, Enger R, Hansson HA, Nagelhus EA, Eide PK. Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus. Glia. 2019;67:91\u2013100.","journal-title":"Glia"},{"key":"1127_CR24","doi-asserted-by":"publisher","first-page":"12586","DOI":"10.1523\/JNEUROSCI.1620-16.2016","volume":"36","author":"X Wang","year":"2016","unstructured":"Wang X, Zhou Y, Wang J, Tseng IC, Huang T, Zhao Y, et al. SNX27 deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis. J Neurosci. 2016;36:12586\u201397.","journal-title":"J Neurosci"},{"key":"1127_CR25","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/ncb2721","volume":"15","author":"F Steinberg","year":"2013","unstructured":"Steinberg F, Gallon M, Winfield M, Thomas EC, Bell AJ, Heesom KJ, et al. A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. Nat Cell Biol. 2013;15:461\u201371.","journal-title":"Nat Cell Biol"},{"key":"1127_CR26","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41580-018-0053-7","volume":"19","author":"PJ Cullen","year":"2018","unstructured":"Cullen PJ, Steinberg F. To degrade or not to degrade: mechanisms and significance of endocytic recycling. Nat Rev Mol Cell Biol. 2018;19:679\u201396.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1127_CR27","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3389\/fnagi.2018.00079","volume":"10","author":"H Zhang","year":"2018","unstructured":"Zhang H, Huang T, Hong Y, Yang W, Zhang X, Luo H, et al. The retromer complex and sorting nexins in neurodegenerative diseases. Front Aging Neurosci. 2018;10:79.","journal-title":"Front Aging Neurosci"},{"key":"1127_CR28","doi-asserted-by":"publisher","first-page":"40048","DOI":"10.1074\/jbc.M005261200","volume":"275","author":"T Iglesias","year":"2000","unstructured":"Iglesias T, Cabrera-Poch N, Mitchell MP, Naven TJ, Rozengurt E, Schiavo G. Identification and cloning of Kidins220, a novel neuronal substrate of protein kinase D. J Biol Chem. 2000;275:40048\u201356.","journal-title":"J Biol Chem"},{"key":"1127_CR29","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1523\/JNEUROSCI.21-01-00176.2001","volume":"21","author":"H Kong","year":"2001","unstructured":"Kong H, Boulter J, Weber JL, Lai C, Chao MV. An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors. J Neurosci. 2001;21:176\u201385.","journal-title":"J Neurosci"},{"key":"1127_CR30","first-page":"1845","volume":"125","author":"VE Neubrand","year":"2012","unstructured":"Neubrand VE, Cesca F, Benfenati F, Schiavo G. Kidins220\/ARMS as a functional mediator of multiple receptor signalling pathways. J Cell Sci. 2012;125:1845\u201354.","journal-title":"J Cell Sci"},{"key":"1127_CR31","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3389\/fncel.2016.00068","volume":"10","author":"J Scholz-Starke","year":"2016","unstructured":"Scholz-Starke J, Cesca F. Stepping out of the shade: control of neuronal activity by the scaffold protein kidins220\/ARMS. Front Cell Neurosci. 2016;10:68.","journal-title":"Front Cell Neurosci"},{"key":"1127_CR32","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1093\/hmg\/dds446","volume":"22","author":"C Lopez-Menendez","year":"2013","unstructured":"Lopez-Menendez C, Gamir-Morralla A, Jurado-Arjona J, Higuero AM, Campanero MR, Ferrer I, et al. Kidins220 accumulates with tau in human Alzheimer\u2019s disease and related models: modulation of its calpain-processing by GSK3beta\/PP1 imbalance. Hum Mol Genet. 2013;22:466\u201382.","journal-title":"Hum Mol Genet"},{"key":"1127_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.307","volume":"6","author":"A Gamir-Morralla","year":"2015","unstructured":"Gamir-Morralla A, Lopez-Menendez C, Ayuso-Dolado S, Tejeda GS, Montaner J, Rosell A, et al. Development of a neuroprotective peptide that preserves survival pathways by preventing Kidins220\/ARMS calpain processing induced by excitotoxicity. Cell Death Dis. 2015;6:e1939.","journal-title":"Cell Death Dis"},{"key":"1127_CR34","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.3233\/JAD-160639","volume":"55","author":"A Gamir-Morralla","year":"2017","unstructured":"Gamir-Morralla A, Belbin O, Fortea J, Alcolea D, Ferrer I, Lleo A, et al. Kidins220 correlates with Tau in alzheimer\u2019s disease brain and cerebrospinal fluid. J Alzheimers Dis. 2017;55:1327\u201333.","journal-title":"J Alzheimers Dis"},{"key":"1127_CR35","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/bpa.12761","volume":"30","author":"A Sebastian-Serrano","year":"2020","unstructured":"Sebastian-Serrano A, Simon-Garcia A, Belmonte-Alfaro A, Pose-Utrilla J, Santos-Galindo M, Del Puerto A, et al. Differential regulation of Kidins220 isoforms in Huntington\u2019s disease. Brain Pathol. 2020;30:120\u201336.","journal-title":"Brain Pathol"},{"key":"1127_CR36","doi-asserted-by":"publisher","first-page":"5415","DOI":"10.1523\/JNEUROSCI.1653-17.2018","volume":"38","author":"S Lopez-Benito","year":"2018","unstructured":"Lopez-Benito S, Sanchez-Sanchez J, Brito V, Calvo L, Lisa S, Torres-Valle M, et al. Regulation of BDNF release by ARMS\/Kidins220 through modulation of synaptotagmin-IV Levels. J Neurosci. 2018;38:5415\u201328.","journal-title":"J Neurosci"},{"key":"1127_CR37","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.schres.2015.07.002","volume":"168","author":"TM Kranz","year":"2015","unstructured":"Kranz TM, Goetz RR, Walsh-Messinger J, Goetz D, Antonius D, Dolgalev I, et al. Rare variants in the neurotrophin signaling pathway implicated in schizophrenia risk. Schizophr Res. 2015;168:421\u20138.","journal-title":"Schizophr Res"},{"key":"1127_CR38","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.schres.2016.02.031","volume":"172","author":"D Malaspina","year":"2016","unstructured":"Malaspina D, Kranz TM, Heguy A, Harroch S, Mazgaj R, Rothman K, et al. Prefrontal neuronal integrity predicts symptoms and cognition in schizophrenia and is sensitive to genetic heterogeneity. Schizophr Res. 2016;172:94\u2013100.","journal-title":"Schizophr Res"},{"key":"1127_CR39","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.ebiom.2016.03.008","volume":"6","author":"TM Kranz","year":"2016","unstructured":"Kranz TM, Berns A, Shields J, Rothman K, Walsh-Messinger J, Goetz RR, et al. Phenotypically distinct subtypes of psychosis accompany novel or rare variants in four different signaling genes. EBioMedicine. 2016;6:206\u201314.","journal-title":"EBioMedicine"},{"key":"1127_CR40","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.1093\/hmg\/ddw082","volume":"25","author":"DJ Josifova","year":"2016","unstructured":"Josifova DJ, Monroe GR, Tessadori F, de Graaff E, van der Zwaag B, Mehta SG, et al. Heterozygous KIDINS220\/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity. Hum Mol Genet. 2016;25:2158\u201367.","journal-title":"Hum Mol Genet"},{"key":"1127_CR41","doi-asserted-by":"publisher","first-page":"3792","DOI":"10.1093\/hmg\/ddx263","volume":"26","author":"IL Mero","year":"2017","unstructured":"Mero IL, Mork HH, Sheng Y, Blomhoff A, Opheim GL, Erichsen A, et al. Homozygous KIDINS220 loss-of-function variants in fetuses with cerebral ventriculomegaly and limb contractures. Hum Mol Genet. 2017;26:3792\u20136.","journal-title":"Hum Mol Genet"},{"key":"1127_CR42","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.neulet.2005.11.062","volume":"397","author":"G Santpere","year":"2006","unstructured":"Santpere G, Nieto M, Puig B, Ferrer I. Abnormal Sp1 transcription factor expression in Alzheimer disease and tauopathies. Neurosci Lett. 2006;397:30\u20134.","journal-title":"Neurosci Lett"},{"key":"1127_CR43","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/cdd.2011.141","volume":"19","author":"F Cesca","year":"2012","unstructured":"Cesca F, Yabe A, Spencer-Dene B, Scholz-Starke J, Medrihan L, Maden CH, et al. Kidins220\/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems. Cell Death Differ. 2012;19:194\u2013208.","journal-title":"Cell Death Differ"},{"key":"1127_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.108","volume":"2","author":"F Cesca","year":"2011","unstructured":"Cesca F, Yabe A, Spencer-Dene B, Arrigoni A, Al-Qatari M, Henderson D, et al. Kidins220\/ARMS is an essential modulator of cardiovascular and nervous system development. Cell Death Dis. 2011;2:e226.","journal-title":"Cell Death Dis"},{"key":"1127_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1766-z","volume":"10","author":"C Lopez-Menendez","year":"2019","unstructured":"Lopez-Menendez C, Simon-Garcia A, Gamir-Morralla A, Pose-Utrilla J, Lujan R, Mochizuki N, et al. Excitotoxic targeting of Kidins220 to the Golgi apparatus precedes calpain cleavage of Rap1-activation complexes. Cell Death Dis. 2019;10:535.","journal-title":"Cell Death Dis"},{"key":"1127_CR46","doi-asserted-by":"crossref","unstructured":"Mirzadeh Z, Doetsch F, Sawamoto K, Wichterle H, Alvarez-Buylla A. The subventricular zone en-face: wholemount staining and ependymal flow. J Vis Exp. 2010; J Vis Exp. 2010; 39:e1938.","DOI":"10.3791\/1938-v"},{"key":"1127_CR47","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00401-009-0624-y","volume":"119","author":"MR Del Bigio","year":"2010","unstructured":"Del Bigio MR. Ependymal cells: biology and pathology. Acta Neuropathol. 2010;119:55\u201373.","journal-title":"Acta Neuropathol"},{"key":"1127_CR48","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00401-012-0992-6","volume":"124","author":"R Roales-Bujan","year":"2012","unstructured":"Roales-Bujan R, Paez P, Guerra M, Rodriguez S, Vio K, Ho-Plagaro A, et al. Astrocytes acquire morphological and functional characteristics of ependymal cells following disruption of ependyma in hydrocephalus. Acta Neuropathol. 2012;124:531\u201346.","journal-title":"Acta Neuropathol"},{"key":"1127_CR49","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/glia.20445","volume":"55","author":"E Raponi","year":"2007","unstructured":"Raponi E, Agenes F, Delphin C, Assard N, Baudier J, Legraverend C, et al. S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage. Glia. 2007;55:165\u201377.","journal-title":"Glia"},{"key":"1127_CR50","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.1242\/dev.041129","volume":"136","author":"BV Jacquet","year":"2009","unstructured":"Jacquet BV, Salinas-Mondragon R, Liang H, Therit B, Buie JD, Dykstra M, et al. FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain. Development. 2009;136:4021\u201331.","journal-title":"Development"},{"key":"1127_CR51","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.celrep.2019.01.088","volume":"27","author":"SA Redmond","year":"2019","unstructured":"Redmond SA, Figueres-Onate M, Obernier K, Nascimento MA, Parraguez JI, Lopez-Mascaraque L, et al. Development of ependymal and postnatal neural stem cells and their origin from a common embryonic progenitor. Cell Rep. 2019;27:429\u201341. e423","journal-title":"Cell Rep"},{"key":"1127_CR52","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.1073\/pnas.1012867108","volume":"108","author":"V Benfenati","year":"2011","unstructured":"Benfenati V, Caprini M, Dovizio M, Mylonakou MN, Ferroni S, Ottersen OP, et al. An aquaporin-4\/transient receptor potential vanilloid 4 (AQP4\/TRPV4) complex is essential for cell-volume control in astrocytes. Proc Natl Acad Sci U.S.A. 2011;108:2563\u20138.","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"1127_CR53","doi-asserted-by":"publisher","first-page":"7008","DOI":"10.1093\/emboj\/20.24.7008","volume":"20","author":"R Madrid","year":"2001","unstructured":"Madrid R, Le Maout S, Barrault MB, Janvier K, Benichou S, Merot J. Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes. EMBO J. 2001;20:7008\u201321.","journal-title":"EMBO J"},{"key":"1127_CR54","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1038\/ncb3610","volume":"19","author":"KE McNally","year":"2017","unstructured":"McNally KE, Faulkner R, Steinberg F, Gallon M, Ghai R, Pim D, et al. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017;19:1214\u201325.","journal-title":"Nat Cell Biol"},{"key":"1127_CR55","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/nsmb.3290","volume":"23","author":"T Clairfeuille","year":"2016","unstructured":"Clairfeuille T, Mas C, Chan AS, Yang Z, Tello-Lafoz M, Chandra M, et al. A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nat Struct Mol Biol. 2016;23:921\u201332.","journal-title":"Nat Struct Mol Biol"},{"key":"1127_CR56","doi-asserted-by":"publisher","first-page":"14108","DOI":"10.1073\/pnas.241508198","volume":"98","author":"JD Neely","year":"2001","unstructured":"Neely JD, Amiry-Moghaddam M, Ottersen OP, Froehner SC, Agre P, Adams ME. Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc Natl Acad Sci U.S.A. 2001;98:14108\u201313.","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"1127_CR57","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1046\/j.1365-2443.2002.00553.x","volume":"7","author":"K Nakahama","year":"2002","unstructured":"Nakahama K, Fujioka A, Nagano M, Satoh S, Furukawa K, Sasaki H, et al. A role of the C-terminus of aquaporin 4 in its membrane expression in cultured astrocytes. Genes Cells. 2002;7:731\u201341.","journal-title":"Genes Cells"},{"key":"1127_CR58","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.neuroscience.2009.04.044","volume":"162","author":"X Li","year":"2009","unstructured":"Li X, Kong H, Wu W, Xiao M, Sun X, Hu G. Aquaporin-4 maintains ependymal integrity in adult mice. Neuroscience. 2009;162:67\u201377.","journal-title":"Neuroscience"},{"key":"1127_CR59","doi-asserted-by":"publisher","first-page":"3862","DOI":"10.1523\/JNEUROSCI.1520-19.2020","volume":"40","author":"KY Wu","year":"2020","unstructured":"Wu KY, Tang FL, Lee D, Zhao Y, Song H, Zhu XJ, et al. Ependymal Vps35 promotes ependymal cell differentiation and survival, suppresses microglial activation, and prevents neonatal hydrocephalus. J Neurosci. 2020;40:3862\u201379.","journal-title":"J Neurosci"},{"key":"1127_CR60","doi-asserted-by":"crossref","unstructured":"Jaudon F, Chiacchiarettla M, Albini M, Ferroni S, Benfenati F, Cesca F. Kidins220\/ARMS controls astrocyte calcium signaling and neuron-astrocyte communication. Cell Death Differ. 2020;27:1505\u201319.","DOI":"10.1038\/s41418-019-0431-5"},{"key":"1127_CR61","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1038\/ncb1627","volume":"9","author":"Z Balklava","year":"2007","unstructured":"Balklava Z, Pant S, Fares H, Grant BD. Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nat Cell Biol. 2007;9:1066\u201373.","journal-title":"Nat Cell Biol"},{"key":"1127_CR62","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1016\/j.celrep.2017.10.053","volume":"21","author":"SR Shinde","year":"2017","unstructured":"Shinde SR, Maddika S. PTEN regulates glucose transporter recycling by impairing SNX27 retromer assembly. Cell Rep. 2017;21:1655\u201366.","journal-title":"Cell Rep"},{"key":"1127_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12309-z","volume":"10","author":"A Stangl","year":"2019","unstructured":"Stangl A, Elliott PR, Pinto-Fernandez A, Bonham S, Harrison L, Schaub A, et al. Regulation of the endosomal SNX27-retromer by OTULIN. Nat Commun. 2019;10:4320.","journal-title":"Nat Commun"},{"key":"1127_CR64","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1093\/brain\/awx191","volume":"140","author":"G Ringstad","year":"2017","unstructured":"Ringstad G, Vatnehol SAS, Eide PK. Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain. 2017;140:2691\u2013705.","journal-title":"Brain"},{"key":"1127_CR65","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1177\/0271678X18760974","volume":"39","author":"PK Eide","year":"2019","unstructured":"Eide PK, Ringstad G. Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: a glymphatic magnetic resonance imaging study. J Cereb Blood Flow Metab. 2019;39:1355\u201368.","journal-title":"J Cereb Blood Flow Metab"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01127-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01127-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01127-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T05:11:16Z","timestamp":1675314676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01127-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":65,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["1127"],"URL":"https:\/\/doi.org\/10.1038\/s41380-021-01127-9","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"assertion":[{"value":"14 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}