{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:15:39Z","timestamp":1793394939710,"version":"4.5.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T00:00:00Z","timestamp":1439856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1005454","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T14:02:05Z","timestamp":1439906525000},"page":"e1005454","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":137,"title":["In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11"],"prefix":"10.1371","volume":"11","author":[{"given":"Rita-Eva","family":"Varga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukhran","family":"Khundadze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Damme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandor","family":"Nietzsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Stauber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Christopher","family":"Hennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Franzka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje K.","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Kessels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Biskup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Jentsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Qualmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Braulke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Kurth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1055\/s-0034-1386767","article-title":"Hereditary spastic paraplegia: clinical principles and genetic advances","volume":"34","author":"JK Fink","year":"2014","journal-title":"Semin Neurol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1126\/science.1247363","article-title":"Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders","volume":"343","author":"G Novarino","year":"2014","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/brain\/awu121","article-title":"Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48","volume":"137","author":"V Pensato","year":"2014","journal-title":"Brain"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/ng1980","article-title":"Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum","volume":"39","author":"G Stevanin","year":"2007","journal-title":"Nat Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.ajhg.2008.03.004","article-title":"Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome","volume":"82","author":"S Hanein","year":"2008","journal-title":"Am J Hum Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"e1000408","DOI":"10.1371\/journal.pbio.1000408","article-title":"A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia","volume":"8","author":"M Slabicki","year":"2010","journal-title":"PLoS Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e1001170","DOI":"10.1371\/journal.pbio.1001170","article-title":"The fifth adaptor protein complex","volume":"9","author":"J Hirst","year":"2011","journal-title":"PLoS Biol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/tra.12028","article-title":"Adaptor Protein Complexes AP-4 and AP-5: New Players in Endosomal Trafficking and Progressive Spastic Paraplegia","volume":"14","author":"J Hirst","year":"2013","journal-title":"Traffic"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/ncb2036","article-title":"PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody","volume":"12","author":"AP Sagona","year":"2010","journal-title":"Nat Cell Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1093\/brain\/awt227","article-title":"Defective autophagy in spastizin mutated patients with hereditary spastic paraparesis type 15","volume":"136","author":"C Vantaggiato","year":"2013","journal-title":"Brain"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1093\/hmg\/ddu200","article-title":"Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia","volume":"23","author":"F Perez-Branguli","year":"2014","journal-title":"Hum Mol Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1091\/mbc.E13-03-0170","article-title":"Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15","volume":"24","author":"J Hirst","year":"2013","journal-title":"Mol Biol Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e1003988","DOI":"10.1371\/journal.pgen.1003988","article-title":"A Hereditary Spastic Paraplegia Mouse Model Supports a Role of ZFYVE26\/SPASTIZIN for the Endolysosomal System","volume":"9","author":"M Khundadze","year":"2013","journal-title":"PLoS Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/acn3.64","article-title":"Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11","volume":"1","author":"B Renvoise","year":"2014","journal-title":"Ann Clin Transl Neurol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1172\/JCI77598","article-title":"Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation","volume":"124","author":"J Chang","year":"2014","journal-title":"J Clin Invest"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.tibs.2013.12.001","article-title":"At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy","volume":"39","author":"HM Shen","year":"2014","journal-title":"Trends Biochem Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.conb.2008.05.006","article-title":"The determination of projection neuron identity in the developing cerebral cortex","volume":"18","author":"DP Leone","year":"2008","journal-title":"Curr Opin Neurobiol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nrn3586","article-title":"Molecular logic of neocortical projection neuron specification, development and diversity","volume":"14","author":"LC Greig","year":"2013","journal-title":"Nat Rev Neurosci"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.nbd.2012.07.003","article-title":"Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish","volume":"48","author":"E Martin","year":"2012","journal-title":"Neurobiol Dis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: renovation of cells and tissues","volume":"147","author":"N Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1136\/jnnp.2008.167528","article-title":"Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia","volume":"80","author":"R Schule","year":"2009","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1093\/emboj\/cdg519","article-title":"Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold","volume":"22","author":"T Boettger","year":"2003","journal-title":"EMBO J"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0006-8993(82)90513-3","article-title":"Deficiency of corpus callosum varies with strain and supplier of the mice","volume":"239","author":"D Wahlsten","year":"1982","journal-title":"Brain Res"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1172\/JCI65665","article-title":"A spastic paraplegia mouse model reveals REEP1-dependent ER shaping","volume":"123","author":"C Beetz","year":"2013","journal-title":"J Clin Invest"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1172\/JCI200420138","article-title":"Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport","volume":"113","author":"F Ferreirinha","year":"2004","journal-title":"J Clin Invest"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1093\/hmg\/ddl431","article-title":"A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition","volume":"15","author":"A Tarrade","year":"2006","journal-title":"Hum Mol Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/glia.20207","article-title":"Astrocyte activation and reactive gliosis","volume":"50","author":"M Pekny","year":"2005","journal-title":"Glia"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.bbadis.2013.01.019","article-title":"Cell biology and function of neuronal ceroid lipofuscinosis-related proteins","volume":"1832","author":"K Kollmann","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/ana.21310","article-title":"Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia","volume":"62","author":"U Hehr","year":"2007","journal-title":"Ann Neurol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"849","DOI":"10.4161\/auto.6845","article-title":"Does bafilomycin A1 block the fusion of autophagosomes with lysosomes?","volume":"4","author":"DJ Klionsky","year":"2008","journal-title":"Autophagy"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature04724","article-title":"Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice","volume":"441","author":"T Hara","year":"2006","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nature04723","article-title":"Loss of autophagy in the central nervous system causes neurodegeneration in mice","volume":"441","author":"M Komatsu","year":"2006","journal-title":"Nature"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"20483","DOI":"10.1074\/jbc.M602180200","article-title":"Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis","volume":"281","author":"Y Cao","year":"2006","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/S0002-9440(10)61253-9","article-title":"Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease)","volume":"167","author":"M Koike","year":"2005","journal-title":"Am J Pathol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrm3565","article-title":"Signals from the lysosome: a control centre for cellular clearance and energy metabolism","volume":"14","author":"C Settembre","year":"2013","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrm2745","article-title":"Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function","volume":"10","author":"P Saftig","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nature09076","article-title":"Termination of autophagy and reformation of lysosomes regulated by mTOR","volume":"465","author":"L Yu","year":"2010","journal-title":"Nature"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1002\/emmm.201201527","article-title":"A mouse model for distal renal tubular acidosis reveals a previously unrecognized role of the V-ATPase a4 subunit in the proximal tubule","volume":"4","author":"JC Hennings","year":"2012","journal-title":"EMBO Mol Med"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1093\/brain\/aws209","article-title":"Lysosomal dysfunction causes neurodegeneration in mucolipidosis II &apos;knock-in&apos; mice","volume":"135","author":"K Kollmann","year":"2012","journal-title":"Brain"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1161\/01.RES.0000204449.83861.22","article-title":"Neurogenic mechanisms contribute to hypertension in mice with disruption of the K-Cl cotransporter KCC3","volume":"98","author":"MB Rust","year":"2006","journal-title":"Circ Res"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"13854","DOI":"10.1073\/pnas.0606137103","article-title":"Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6","volume":"103","author":"M Poet","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/nmeth.2047","article-title":"BioImageXD: an open, general-purpose and high-throughput image-processing platform","volume":"9","author":"P Kankaanpaa","year":"2012","journal-title":"Nat Methods"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1126\/science.1188072","article-title":"Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation","volume":"328","author":"S Weinert","year":"2010","journal-title":"Science"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1005454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T17:35:40Z","timestamp":1540316140000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1005454"}},"subtitle":[],"editor":[{"given":"Gregory A.","family":"Cox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,8,18]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,8,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1005454","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725726134.793513491","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,18]]}}}