{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:36:00Z","timestamp":1792787760085,"version":"4.5.0"},"reference-count":82,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["Bioscience Research Grants 2026024988"],"award-info":[{"award-number":["Bioscience Research Grants 2026024988"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Akiyama Life Science Foundation","award":["2026"],"award-info":[{"award-number":["2026"]}],"id":[{"id":"https:\/\/ror.org\/04198sg47","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Neuroscientist"],"abstract":"<jats:p>\n                    The neuronal endoplasmic reticulum (ER) forms a continuous membrane network that extends throughout the soma, dendrites, axons, and synaptic compartments. Although traditionally viewed as a structurally continuous intracellular organelle, recent advances in volume electron microscopy, super-resolution imaging, and live-cell functional analyses have revealed that the ER is highly compartmentalized into specialized structural and molecular domains. These domains organize local Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release, store refilling, luminal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    redistribution, and inter-organelle communication through membrane contact sites, thereby enabling the diverse physiological functions of the ER. Emerging evidence further indicates that ER topology is a fundamental determinant of diverse ER functions and that disruption of ER architecture is increasingly implicated in the pathogenesis of neurological disorders. In this review, I first summarize the ultrastructural organization of the neuronal ER based on representative electron microscopy observations and then discuss how spatial compartmentalization provides an organizational principle linking ER structure to intracellular signaling, neuronal homeostasis, and neurological disorders.\n                  <\/jats:p>","DOI":"10.1177\/10738584261488785","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:19:22Z","timestamp":1791436762000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial Compartmentalization of the Neuronal Endoplasmic Reticulum: Structural Basis of Calcium Signaling and Cellular Homeostasis"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-9349","authenticated-orcid":false,"given":"Miwako","family":"Yamasaki","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"crossref","unstructured":"Ageta-Ishihara N et al. 2025. Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines. Cell Rep. 44:115352. https:\/\/doi.org\/10.1016\/j.celrep.2025.115352","DOI":"10.1016\/j.celrep.2025.115352"},{"key":"e_1_3_3_3_1","doi-asserted-by":"crossref","unstructured":"Apicco DJ et al. 2021. The Parkinson\u2019s disease-associated gene ITPKB protects against alpha-synuclein aggregation by regulating ER-to-mitochondria calcium release. Proc Natl Acad Sci U S A. 118:e2006476118. https:\/\/doi.org\/10.1073\/pnas.2006476118","DOI":"10.1073\/pnas.2006476118"},{"key":"e_1_3_3_4_1","doi-asserted-by":"crossref","unstructured":"Area-Gomez E Schon EA. 2017. On the pathogenesis of Alzheimer\u2019s disease: the MAM hypothesis. FASEB J. 31:864\u2013867. https:\/\/doi.org\/10.1096\/fj.201601309","DOI":"10.1096\/fj.201601309"},{"key":"e_1_3_3_5_1","doi-asserted-by":"crossref","unstructured":"Area-Gomez E et al. 2009. Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am J Pathol. 175:1810\u20131816. https:\/\/doi.org\/10.2353\/ajpath.2009.090219","DOI":"10.2353\/ajpath.2009.090219"},{"key":"e_1_3_3_6_1","doi-asserted-by":"crossref","unstructured":"Area-Gomez E et al. 2012. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 31:4106\u20134123. https:\/\/doi.org\/10.1038\/emboj.2012.202","DOI":"10.1038\/emboj.2012.202"},{"key":"e_1_3_3_7_1","doi-asserted-by":"crossref","unstructured":"Baumann O Walz B. 2001. Endoplasmic reticulum of animal cells and its organization into structural and functional domains. Int Rev Cytol. 205:149\u2013214. https:\/\/doi.org\/10.1016\/s0074-7696(01)05004-5","DOI":"10.1016\/S0074-7696(01)05004-5"},{"key":"e_1_3_3_8_1","doi-asserted-by":"crossref","unstructured":"Beetz C et al. 2013. A spastic paraplegia mouse model reveals REEP1-dependent ER shaping. J Clin Invest. 123:4273\u20134282. https:\/\/doi.org\/10.1172\/JCI65665","DOI":"10.1172\/JCI65665"},{"key":"e_1_3_3_9_1","doi-asserted-by":"crossref","unstructured":"Benedeczky I Moln\u00e1r E Somogyi P. 1994. The cisternal organelle as a Ca2+-storing compartment associated with GABAergic synapses in the axon initial segment of hippocampal pyramidal neurones. Exp Brain Res. 101:216\u2013230. https:\/\/doi.org\/10.1007\/BF00228742","DOI":"10.1007\/BF00228742"},{"key":"e_1_3_3_10_1","doi-asserted-by":"crossref","unstructured":"Benedetti L et al. 2025. Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites. Cell. 188:484.e22\u2013500.e22. https:\/\/doi.org\/10.1016\/j.cell.2024.11.029","DOI":"10.1016\/j.cell.2024.11.029"},{"key":"e_1_3_3_11_1","doi-asserted-by":"crossref","unstructured":"Blackstone C O\u2019Kane CJ Reid E. 2011. Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci. 12:31\u201342. https:\/\/doi.org\/10.1038\/nrn2946","DOI":"10.1038\/nrn2946"},{"key":"e_1_3_3_12_1","doi-asserted-by":"crossref","unstructured":"Broadwell RD Cataldo AM. 1983. The neuronal endoplasmic reticulum: its cytochemistry and contribution to the endomembrane system. I. Cell bodies and dendrites. J Histochem Cytochem. 31:1077\u20131088. https:\/\/doi.org\/10.1177\/31.9.6309951","DOI":"10.1177\/31.9.6309951"},{"key":"e_1_3_3_13_1","doi-asserted-by":"crossref","unstructured":"Carvalhais LG Kole K Kuijpers M. 2026. The diverse forms and roles of the neuronal endoplasmic reticulum. Nat Rev Neurosci. 27:260\u2013277. https:\/\/doi.org\/10.1038\/s41583-025-01016-y","DOI":"10.1038\/s41583-025-01016-y"},{"key":"e_1_3_3_14_1","doi-asserted-by":"crossref","unstructured":"Chen-Engerer HJ et al. 2019. Two types of functionally distinct Ca2+ stores in hippocampal neurons. Nat Commun. 10:3223. https:\/\/doi.org\/10.1038\/s41467-019-11207-8","DOI":"10.1038\/s41467-019-11207-8"},{"key":"e_1_3_3_15_1","doi-asserted-by":"crossref","unstructured":"Cherubini M Lopez-Molina L Gines S. 2020. Mitochondrial fission in Huntington\u2019s disease mouse striatum disrupts ER-mitochondria contacts leading to disturbances in Ca2+ efflux and Reactive Oxygen Species (ROS) homeostasis. Neurobiol Dis. 136:104741. https:\/\/doi.org\/10.1016\/j.nbd.2020.104741","DOI":"10.1016\/j.nbd.2020.104741"},{"key":"e_1_3_3_16_1","doi-asserted-by":"crossref","unstructured":"Crapart CC et al. 2024. Luminal transport through intact endoplasmic reticulum limits the magnitude of localized Ca2+ signals. Proc Natl Acad Sci U S A. 121:e2312172121. https:\/\/doi.org\/10.1073\/pnas.2312172121","DOI":"10.1073\/pnas.2312172121"},{"key":"e_1_3_3_17_1","doi-asserted-by":"crossref","unstructured":"Cui-Wang T et al. 2012. Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites. Cell. 148:309\u2013321. https:\/\/doi.org\/10.1016\/j.cell.2011.11.056","DOI":"10.1016\/j.cell.2011.11.056"},{"key":"e_1_3_3_18_1","doi-asserted-by":"crossref","unstructured":"Dreser A et al. 2017. The ALS-linked E102Q mutation in Sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins. Cell Death Differ. 24:1655\u20131671. https:\/\/doi.org\/10.1038\/cdd.2017.88","DOI":"10.1038\/cdd.2017.88"},{"key":"e_1_3_3_19_1","doi-asserted-by":"crossref","unstructured":"Droz B Rambourg A Koenig HL. 1975. The smooth endoplasmic reticulum: structure and role in the renewal of axonal membrane and synaptic vesicles by fast axonal transport. Brain Res. 93:1\u201313. https:\/\/doi.org\/10.1016\/0006-8993(75)90282-6","DOI":"10.1016\/0006-8993(75)90282-6"},{"key":"e_1_3_3_20_1","doi-asserted-by":"crossref","unstructured":"Dubes S et al. 2022. miR-124-dependent tagging of synapses by synaptopodin enables input-specific homeostatic plasticity. EMBO J. 41:e109012. https:\/\/doi.org\/10.15252\/embj.2021109012","DOI":"10.15252\/embj.2021109012"},{"key":"e_1_3_3_21_1","doi-asserted-by":"crossref","unstructured":"Falahati H Wu Y Feuerer V Simon HG De Camilli P. 2022. Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines. Proc Natl Acad Sci U S A. 119:e2203750119. https:\/\/doi.org\/10.1073\/pnas.2203750119","DOI":"10.1073\/pnas.2203750119"},{"key":"e_1_3_3_22_1","doi-asserted-by":"crossref","unstructured":"Gallo A Vannier C Galli T. 2016. Endoplasmic reticulum-plasma membrane associations:structures and functions. Annu Rev Cell Dev Biol. 32:279\u2013301. https:\/\/doi.org\/10.1146\/annurev-cellbio-111315-125024","DOI":"10.1146\/annurev-cellbio-111315-125024"},{"key":"e_1_3_3_23_1","doi-asserted-by":"crossref","unstructured":"Garaschuk O Yaari Y Konnerth A. 1997. Release and sequestration of calcium by ryanodine-sensitive stores in rat hippocampal neurones. J Physiol. 502 (Pt. 1):13\u201330. https:\/\/doi.org\/10.1111\/j.1469-7793.1997.013bl.x","DOI":"10.1111\/j.1469-7793.1997.013bl.x"},{"key":"e_1_3_3_24_1","doi-asserted-by":"crossref","unstructured":"Golovina VA Blaustein MP. 1997. Spatially and functionally distinct Ca2+ stores in sarcoplasmic and endoplasmic reticulum. Science. 275:1643\u20131648. https:\/\/doi.org\/10.1126\/science.275.5306.1643","DOI":"10.1126\/science.275.5306.1643"},{"key":"e_1_3_3_25_1","doi-asserted-by":"crossref","unstructured":"Golovina VA Blaustein MP. 2000. Unloading and refilling of two classes of spatially resolved endoplasmic reticulum Ca2+ stores in astrocytes. Glia. 31:15\u201328. https:\/\/doi.org\/10.1002\/(sici)1098-1136(200007)31:1<15::aid-glia20>3.0.co;2-h","DOI":"10.1002\/(SICI)1098-1136(200007)31:1<15::AID-GLIA20>3.0.CO;2-H"},{"key":"e_1_3_3_26_1","doi-asserted-by":"crossref","unstructured":"Goussakov I Miller MB Stutzmann GE. 2010. NMDA-mediated Ca2+ influx drives aberrant ryanodine receptor activation in dendrites of young Alzheimer\u2019s disease mice. J Neurosci. 30:12128\u201312137. https:\/\/doi.org\/10.1523\/JNEUROSCI.2474-10.2010","DOI":"10.1523\/JNEUROSCI.2474-10.2010"},{"key":"e_1_3_3_27_1","doi-asserted-by":"crossref","unstructured":"Harris KM. 2020. Synaptic odyssey. J Neurosci. 40:61\u201380. https:\/\/doi.org\/10.1523\/JNEUROSCI.0735-19.2019","DOI":"10.1523\/JNEUROSCI.0735-19.2019"},{"key":"e_1_3_3_28_1","doi-asserted-by":"crossref","unstructured":"Harris KM Stevens JK. 1988. Dendritic spines of rat cerebellar Purkinje cells: serial electron microscopy with reference to their biophysical characteristics. J Neurosci. 8:4455\u20134469. https:\/\/doi.org\/10.1523\/JNEUROSCI.08-12-04455.1988","DOI":"10.1523\/JNEUROSCI.08-12-04455.1988"},{"key":"e_1_3_3_29_1","doi-asserted-by":"crossref","unstructured":"Hartmann J et al. 2014. STIM1 controls neuronal Ca2+ signaling mGluR1-dependent synaptic transmission and cerebellar motor behavior. Neuron. 82:635\u2013644. https:\/\/doi.org\/10.1016\/j.neuron.2014.03.027","DOI":"10.1016\/j.neuron.2014.03.027"},{"key":"e_1_3_3_30_1","doi-asserted-by":"crossref","unstructured":"He W et al. 2004. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nat Med. 10:959\u2013965. https:\/\/doi.org\/10.1038\/nm1088","DOI":"10.1038\/nm1088"},{"key":"e_1_3_3_31_1","doi-asserted-by":"crossref","unstructured":"Hedskog L et al. 2013. Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer\u2019s disease and related models. Proc Natl Acad Sci U S A. 110:7916\u20137921. https:\/\/doi.org\/10.1073\/pnas.1300677110","DOI":"10.1073\/pnas.1300677110"},{"key":"e_1_3_3_32_1","doi-asserted-by":"crossref","unstructured":"Hirabayashi Y et al. 2017. ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons. Science. 358:623\u2013630. https:\/\/doi.org\/10.1126\/science.aan6009","DOI":"10.1126\/science.aan6009"},{"key":"e_1_3_3_33_1","doi-asserted-by":"crossref","unstructured":"Hoffmann PC et al. 2021. Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids. eLife. 10:e70269. https:\/\/doi.org\/10.7554\/eLife.70269","DOI":"10.7554\/eLife.70269"},{"key":"e_1_3_3_34_1","doi-asserted-by":"crossref","unstructured":"Holbro N Grunditz A Oertner TG. 2009. Differential distribution of endoplasmic reticulum controls metabotropic signaling and plasticity at hippocampal synapses. Proc Natl Acad Sci U S A. 106:15055\u201315060. https:\/\/doi.org\/10.1073\/pnas.0905110106","DOI":"10.1073\/pnas.0905110106"},{"key":"e_1_3_3_35_1","doi-asserted-by":"crossref","unstructured":"Kakizawa S et al. 2007. Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. EMBO J. 26:1924\u20131933. https:\/\/doi.org\/10.1038\/sj.emboj.7601639","DOI":"10.1038\/sj.emboj.7601639"},{"key":"e_1_3_3_36_1","doi-asserted-by":"crossref","unstructured":"Koizumi S et al. 1999. Characterization of elementary Ca2+ release signals in NGF-differentiated PC12 cells and hippocampal neurons. Neuron. 22:125\u2013137. https:\/\/doi.org\/10.1016\/s0896-6273(00)80684-4","DOI":"10.1016\/S0896-6273(00)80684-4"},{"key":"e_1_3_3_37_1","doi-asserted-by":"crossref","unstructured":"Konno T et al. 2024. Endoplasmic reticulum morphology regulation by RTN4 modulates neuronal regeneration by curbing luminal transport. Cell Rep. 43:114357. https:\/\/doi.org\/10.1016\/j.celrep.2024.114357","DOI":"10.1016\/j.celrep.2024.114357"},{"key":"e_1_3_3_38_1","doi-asserted-by":"crossref","unstructured":"Kornak U et al. 2014. Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. Brain. 137:683\u2013692. https:\/\/doi.org\/10.1093\/brain\/awt357","DOI":"10.1093\/brain\/awt357"},{"key":"e_1_3_3_39_1","doi-asserted-by":"crossref","unstructured":"Kostyuk PG Kirischuk SI. 1993. Spatial heterogeneity of caffeine- and inositol 1 4 5-trisphosphate-induced Ca2+ transients in isolated snail neurons. Neuroscience. 53:943\u2013947. https:\/\/doi.org\/10.1016\/0306-4522(93)90479-y","DOI":"10.1016\/0306-4522(93)90479-Y"},{"key":"e_1_3_3_40_1","doi-asserted-by":"crossref","unstructured":"Lacampagne A et al. 2017. Post-translational remodeling of ryanodine receptor induces calcium leak leading to Alzheimer\u2019s disease-like pathologies and cognitive deficits. Acta Neuropathol. 134:749\u2013767. https:\/\/doi.org\/10.1007\/s00401-017-1733-7","DOI":"10.1007\/s00401-017-1733-7"},{"key":"e_1_3_3_41_1","doi-asserted-by":"crossref","unstructured":"LaFerla FM. 2002. Calcium dyshomeostasis and intracellular signalling in Alzheimer\u2019s disease. Nat Rev Neurosci. 3:862\u2013872. https:\/\/doi.org\/10.1038\/nrn960","DOI":"10.1038\/nrn960"},{"key":"e_1_3_3_42_1","doi-asserted-by":"crossref","unstructured":"Lindsey JD Ellisman MH. 1985. The neuronal endomembrane system. III. The origins of the axoplasmic reticulum and discrete axonal cisternae at the axon hillock. J Neurosci. 5:3135\u20133144. https:\/\/doi.org\/10.1523\/JNEUROSCI.05-12-03135.1985","DOI":"10.1523\/JNEUROSCI.05-12-03135.1985"},{"key":"e_1_3_3_43_1","doi-asserted-by":"crossref","unstructured":"Miyata M et al. 2011. A role for myosin Va in cerebellar plasticity and motor learning: a possible mechanism underlying neurological disorder in myosin Va disease. J Neurosci. 31:6067\u20136078. https:\/\/doi.org\/10.1523\/JNEUROSCI.5651-10.2011","DOI":"10.1523\/JNEUROSCI.5651-10.2011"},{"key":"e_1_3_3_44_1","doi-asserted-by":"crossref","unstructured":"Nitta A et al. 2025. Molecular and anatomical strengthening of \u201cwinner\u201d climbing fiber synapses in developing mouse Purkinje cells. J Neurosci. 45:e2156242025. https:\/\/doi.org\/10.1523\/JNEUROSCI.2156-24.2025","DOI":"10.1523\/JNEUROSCI.2156-24.2025"},{"key":"e_1_3_3_45_1","doi-asserted-by":"crossref","unstructured":"Nomura S Yamasaki M Miyazaki T Konno K Watanabe M. 2025. Preferential localization of STIM1 to dendritic subsurface ER structures in mouse Purkinje cells. J Neurosci. 45:e1829242025. https:\/\/doi.org\/10.1523\/JNEUROSCI.1829-24.2025","DOI":"10.1523\/JNEUROSCI.1829-24.2025"},{"key":"e_1_3_3_46_1","doi-asserted-by":"crossref","unstructured":"Okubo Y et al. 2015. Visualization of Ca2+ filling mechanisms upon synaptic inputs in the endoplasmic reticulum of cerebellar Purkinje cells. J Neurosci. 35:15837\u201315846. https:\/\/doi.org\/10.1523\/JNEUROSCI.3487-15.2015","DOI":"10.1523\/JNEUROSCI.3487-15.2015"},{"key":"e_1_3_3_47_1","doi-asserted-by":"crossref","unstructured":"Orantos-Aguilera Y et al. 2026. STIM1-containing contact sites promote direct calcium flux from the endoplasmic reticulum to mitochondria. EMBO J. 45:1760\u20131793. https:\/\/doi.org\/10.1038\/s44318-026-00700-8","DOI":"10.1038\/s44318-026-00700-8"},{"key":"e_1_3_3_48_1","doi-asserted-by":"crossref","unstructured":"Oules B et al. 2012. Ryanodine receptor blockade reduces amyloid-beta load and memory impairments in Tg2576 mouse model of Alzheimer disease. J Neurosci. 32:11820\u201311834. https:\/\/doi.org\/10.1523\/JNEUROSCI.0875-12.2012","DOI":"10.1523\/JNEUROSCI.0875-12.2012"},{"key":"e_1_3_3_49_1","doi-asserted-by":"crossref","unstructured":"Paillusson S et al. 2017. Alpha-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production. Acta Neuropathol. 134:129\u2013149. https:\/\/doi.org\/10.1007\/s00401-017-1704-z","DOI":"10.1007\/s00401-017-1704-z"},{"key":"e_1_3_3_50_1","doi-asserted-by":"crossref","unstructured":"Palade GE. 1955. A small particulate component of the cytoplasm. J Biophys Biochem Cytol. 1:59\u201368. https:\/\/doi.org\/10.1083\/jcb.1.1.59","DOI":"10.1083\/jcb.1.1.59"},{"key":"e_1_3_3_51_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.1.1.69"},{"key":"e_1_3_3_52_1","doi-asserted-by":"crossref","unstructured":"Park SH Zhu PP Parker RL Blackstone C. 2010. Hereditary spastic paraplegia proteins REEP1 spastin and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest. 120:1097\u20131110. https:\/\/doi.org\/10.1172\/JCI40979","DOI":"10.1172\/JCI40979"},{"key":"e_1_3_3_53_1","doi-asserted-by":"crossref","unstructured":"Perez-Alvarez A et al. 2020. Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses. Nat Commun. 11:5083. https:\/\/doi.org\/10.1038\/s41467-020-18889-5","DOI":"10.1038\/s41467-020-18889-5"},{"key":"e_1_3_3_54_1","unstructured":"Peters A Palay SL Webster HD. 1991. The fine structure of the nervous system. 3rd ed. Oxford University Press."},{"key":"e_1_3_3_55_1","doi-asserted-by":"crossref","unstructured":"Phillips MJ Voeltz GK. 2016. Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol. 17:69\u201382. https:\/\/doi.org\/10.1038\/nrm.2015.8","DOI":"10.1038\/nrm.2015.8"},{"key":"e_1_3_3_56_1","doi-asserted-by":"crossref","unstructured":"Porter KR Palade GE. 1957. Studies on the endoplasmic reticulum. III. Its form and distribution in striated muscle cells. J Biophys Biochem Cytol. 3:269\u2013300. https:\/\/doi.org\/10.1083\/jcb.3.2.269","DOI":"10.1083\/jcb.3.2.269"},{"key":"e_1_3_3_57_1","doi-asserted-by":"crossref","unstructured":"Rosenbluth J. 1962. Subsurface cisterns and their relationship to the neuronal plasma membrane. J Cell Biol. 13:405\u2013421. https:\/\/doi.org\/10.1083\/jcb.13.3.405","DOI":"10.1083\/jcb.13.3.405"},{"key":"e_1_3_3_58_1","doi-asserted-by":"crossref","unstructured":"Sahu G et al. 2019. Junctophilin proteins tether a Cav1-RyR2-KCa3.1 tripartite complex to regulate neuronal excitability. Cell Rep. 28:2427.e6\u20132442.e6. https:\/\/doi.org\/10.1016\/j.celrep.2019.07.075","DOI":"10.1016\/j.celrep.2019.07.075"},{"key":"e_1_3_3_59_1","doi-asserted-by":"crossref","unstructured":"Sanchez-Ponce D Blazquez-Llorca L DeFelipe J Garrido JJ Munoz A. 2012. Colocalization of alpha-actinin and synaptopodin in the pyramidal cell axon initial segment. Cereb Cortex. 22:1648\u20131661. https:\/\/doi.org\/10.1093\/cercor\/bhr251","DOI":"10.1093\/cercor\/bhr251"},{"key":"e_1_3_3_60_1","doi-asserted-by":"crossref","unstructured":"Satoh T et al. 1990. The inositol 1 4 5 -trisphosphate receptor in cerebellar Purkinje cells: quantitative immunogold labeling reveals concentration in an ER subcompartment. J Cell Biol. 111:615\u2013624. https:\/\/doi.org\/10.1083\/jcb.111.2.615","DOI":"10.1083\/jcb.111.2.615"},{"key":"e_1_3_3_61_1","doi-asserted-by":"crossref","unstructured":"Scorrano L et al. 2019. Coming together to define membrane contact sites. Nat Commun. 10:1287. https:\/\/doi.org\/10.1038\/s41467-019-09253-3","DOI":"10.1038\/s41467-019-09253-3"},{"key":"e_1_3_3_62_1","doi-asserted-by":"crossref","unstructured":"Shibata Y Voeltz GK Rapoport TA. 2006. Rough sheets and smooth tubules. Cell. 126:435\u2013439. https:\/\/doi.org\/10.1016\/j.cell.2006.07.019","DOI":"10.1016\/j.cell.2006.07.019"},{"key":"e_1_3_3_63_1","doi-asserted-by":"crossref","unstructured":"Shilling D et al. 2014. Suppression of InsP3 receptor-mediated Ca2+ signaling alleviates mutant presenilin-linked familial Alzheimer\u2019s disease pathogenesis. J Neurosci. 34:6910\u20136923. https:\/\/doi.org\/10.1523\/JNEUROSCI.5441-13.2014","DOI":"10.1523\/JNEUROSCI.5441-13.2014"},{"key":"e_1_3_3_64_1","doi-asserted-by":"crossref","unstructured":"Spacek J Harris KM. 1997. Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J Neurosci. 17:190\u2013203. https:\/\/doi.org\/10.1523\/JNEUROSCI.17-01-00190.1997","DOI":"10.1523\/JNEUROSCI.17-01-00190.1997"},{"key":"e_1_3_3_65_1","doi-asserted-by":"crossref","unstructured":"Stutzmann GE Caccamo A LaFerla FM Parker I. 2004. Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer\u2019s-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci. 24:508\u2013513. https:\/\/doi.org\/10.1523\/JNEUROSCI.4386-03.2004","DOI":"10.1523\/JNEUROSCI.4386-03.2004"},{"key":"e_1_3_3_66_1","doi-asserted-by":"crossref","unstructured":"Stutzmann GE et al. 2006. Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young adult and aged Alzheimer\u2019s disease mice. J Neurosci. 26:5180\u20135189. https:\/\/doi.org\/10.1523\/JNEUROSCI.0739-06.2006","DOI":"10.1523\/JNEUROSCI.0739-06.2006"},{"key":"e_1_3_3_67_1","doi-asserted-by":"crossref","unstructured":"Takagishi Y et al. 2007. Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats. Dev Neurobiol. 67:909\u2013923. https:\/\/doi.org\/10.1002\/dneu.20375","DOI":"10.1002\/dneu.20375"},{"key":"e_1_3_3_68_1","doi-asserted-by":"crossref","unstructured":"Takei K et al. 1992. Ca2+ stores in Purkinje neurons: endoplasmic reticulum subcompartments demonstrated by the heterogeneous distribution of the InsP3 receptor Ca2+-ATPase and calsequestrin. J Neurosci. 12:489\u2013505. https:\/\/doi.org\/10.1523\/JNEUROSCI.12-02-00489.1992","DOI":"10.1523\/JNEUROSCI.12-02-00489.1992"},{"key":"e_1_3_3_69_1","doi-asserted-by":"crossref","unstructured":"Tang TS et al. 2003. Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1 4 5) triphosphate receptor type 1. Neuron. 39:227\u2013239. https:\/\/doi.org\/10.1016\/s0896-6273(03)00366-0","DOI":"10.1016\/S0896-6273(03)00366-0"},{"key":"e_1_3_3_70_1","doi-asserted-by":"crossref","unstructured":"Tang TS et al. 2005. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington\u2019s disease. Proc Natl Acad Sci U S A. 102:2602\u20132607. https:\/\/doi.org\/10.1073\/pnas.0409402102","DOI":"10.1073\/pnas.0409402102"},{"key":"e_1_3_3_71_1","doi-asserted-by":"crossref","unstructured":"Terasaki M. 2018. Axonal endoplasmic reticulum is very narrow. J Cell Sci. 131:jcs210450. https:\/\/doi.org\/10.1242\/jcs.210450","DOI":"10.1242\/jcs.210450"},{"key":"e_1_3_3_72_1","doi-asserted-by":"crossref","unstructured":"Teuling E et al. 2007. Motor neuron disease-associated mutant vesicle-associated membrane protein-associated protein (VAP) B recruits wild-type VAPs into endoplasmic reticulum-derived tubular aggregates. J Neurosci. 27:9801\u20139815. https:\/\/doi.org\/10.1523\/JNEUROSCI.2661-07.2007","DOI":"10.1523\/JNEUROSCI.2661-07.2007"},{"key":"e_1_3_3_73_1","doi-asserted-by":"crossref","unstructured":"Thibault O Gant JC Landfield PW. 2007. Expansion of the calcium hypothesis of brain aging and Alzheimer\u2019s disease: minding the store. Aging Cell. 6:307\u2013317. https:\/\/doi.org\/10.1111\/j.1474-9726.2007.00295.x","DOI":"10.1111\/j.1474-9726.2007.00295.x"},{"key":"e_1_3_3_74_1","first-page":"141","article-title":"Three-dimensional distribution of smooth endoplasmic reticulum in myelinated axons","volume":"25","author":"Tsukita S","year":"1976","unstructured":"Tsukita S, Ishikawa H. 1976. Three-dimensional distribution of smooth endoplasmic reticulum in myelinated axons. J Electron Microsc (Tokyo) 25:141\u2013149.","journal-title":"J Electron Microsc (Tokyo)"},{"key":"e_1_3_3_75_1","doi-asserted-by":"crossref","unstructured":"Valm AM et al. 2017. Applying systems-level spectral imaging and analysis to reveal the organelle interactome. Nature. 546:162\u2013167. https:\/\/doi.org\/10.1038\/nature22369","DOI":"10.1038\/nature22369"},{"key":"e_1_3_3_76_1","doi-asserted-by":"crossref","unstructured":"Vierra NC et al. 2023. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nat Commun. 14:5231. https:\/\/doi.org\/10.1038\/s41467-023-40930-6","DOI":"10.1038\/s41467-023-40930-6"},{"key":"e_1_3_3_77_1","doi-asserted-by":"crossref","unstructured":"Voeltz GK Sawyer EM Hajnoczky G Prinz WA. 2024. Making the connection: how membrane contact sites have changed our view of organelle biology. Cell. 187:257\u2013270. https:\/\/doi.org\/10.1016\/j.cell.2023.11.040","DOI":"10.1016\/j.cell.2023.11.040"},{"key":"e_1_3_3_78_1","doi-asserted-by":"crossref","unstructured":"Webber EK Fivaz M Stutzmann GE Griffioen G. 2023. Cytosolic calcium: judge jury and executioner of neurodegeneration in Alzheimer\u2019s disease and beyond. Alzheimers Dement. 19:3701\u20133717. https:\/\/doi.org\/10.1002\/alz.13065","DOI":"10.1002\/alz.13065"},{"key":"e_1_3_3_79_1","doi-asserted-by":"crossref","unstructured":"Westrate LM Lee JE Prinz WA Voeltz GK. 2015. Form follows function: the importance of endoplasmic reticulum shape. Annu Rev Biochem. 84:791\u2013811. https:\/\/doi.org\/10.1146\/annurev-biochem-072711-163501","DOI":"10.1146\/annurev-biochem-072711-163501"},{"key":"e_1_3_3_80_1","doi-asserted-by":"crossref","unstructured":"Wu Y et al. 2017. Contacts between the endoplasmic reticulum and other membranes in neurons. Proc Natl Acad Sci U S A. 114:E4859-E4867. https:\/\/doi.org\/10.1073\/pnas.1701078114","DOI":"10.1073\/pnas.1701078114"},{"key":"e_1_3_3_81_1","doi-asserted-by":"crossref","unstructured":"Yamasaki M et al. 2026. mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum. Proc Natl Acad Sci U S A. 123:e2425460123. https:\/\/doi.org\/10.1073\/pnas.2425460123","DOI":"10.1073\/pnas.2425460123"},{"key":"e_1_3_3_82_1","doi-asserted-by":"crossref","unstructured":"Zamponi E Meehl JB Voeltz GK. 2022. The ER ladder is a unique morphological feature of developing mammalian axons. Dev Cell. 57:1369.e6\u20131382.e6. https:\/\/doi.org\/10.1016\/j.devcel.2022.05.002","DOI":"10.1016\/j.devcel.2022.05.002"},{"key":"e_1_3_3_83_1","doi-asserted-by":"crossref","unstructured":"Zhu PP Soderblom C Tao-Cheng JH Stadler J Blackstone C. 2006. SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development. Hum Mol Genet. 15:1343\u20131353. https:\/\/doi.org\/10.1093\/hmg\/ddl054","DOI":"10.1093\/hmg\/ddl054"}],"container-title":["The Neuroscientist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10738584261488785","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10738584261488785","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10738584261488785","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T08:18:33Z","timestamp":1791706713000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10738584261488785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":82,"alternative-id":["10.1177\/10738584261488785"],"URL":"https:\/\/doi.org\/10.1177\/10738584261488785","relation":{},"ISSN":["1073-8584","1089-4098"],"issn-type":[{"value":"1073-8584","type":"print"},{"value":"1089-4098","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"10738584261488785"}}