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dc.contributor.authorCao, Yi
dc.contributor.authorF. Staropoli, John
dc.contributor.authorBiswas, Sunita
dc.contributor.authorA. Espinola, Janice
dc.contributor.authorE. MacDonald, Marcy
dc.contributor.authorLee, Jong-Min
dc.contributor.authorL. Cotman, Susan
dc.date.accessioned2017-05-03T16:03:57Z
dc.date.available2017-05-03T16:03:57Z
dc.date.issued2011
dc.date.modified2011-09-30T04:23:06Z
dc.identifier.issn19326203
dc.identifier.doi10.1371/journal.pone.0017118
dc.identifier.urihttp://hdl.handle.net/10072/41087
dc.description.abstractVariant late-infantile neuronal ceroid lipofuscinosis (vLINCL), caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL), caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6(nclf/nclf) cerebellar cells and compared them to wild-type and CbCln3(?ex7/8/?ex7/8) cerebellar cells. CbCln6(nclf/nclf) cells and CbCln3(?ex7/8/?ex7/8) cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6(nclf/nclf) cells, while fluid-phase endocytosis and LysoTrackerabeled vesicles were decreased in both CbCln6(nclf/nclf) and CbCln3(?ex7/8/?ex7/8) cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3(?ex7/8) and Cln6(nclf) mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent4901010 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrome17118-1
dc.relation.ispartofpagetoe17118-14
dc.relation.ispartofissue2
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume6
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchcode060199
dc.titleDistinct Early Molecular Responses to Mutations Causing vLINCL and JNCL Presage ATP Synthase Subunit C Accumulation in Cerebellar Cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://www.plos.org/journals/license.html
gro.rights.copyright© 2011 Cao et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
gro.date.issued2011
gro.hasfulltextFull Text
gro.griffith.authorBiswas, Sunita


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