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dc.contributor.authorGrigorenko, Anastasia P.
dc.contributor.authorMoliaka, Yuri K.
dc.contributor.authorSoto, Martha C.
dc.contributor.authorMello, Craig C.
dc.contributor.authorRogaev, Evgeny I
dc.date2022-08-11T08:09:36.000
dc.date.accessioned2022-08-23T16:37:03Z
dc.date.available2022-08-23T16:37:03Z
dc.date.issued2004-10-08
dc.date.submitted2009-04-02
dc.identifier.citation<p>Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14955-60. Epub 2004 Oct 6. <a href="http://dx.doi.org/10.1073/pnas.0406462101">Link to article on publisher's site</a></p>
dc.identifier.issn0027-8424 (Print)
dc.identifier.doi10.1073/pnas.0406462101
dc.identifier.pmid15469912
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38927
dc.description.abstractPresenilins (PSs) are required for Notch signaling in the development of vertebrates and invertebrates. Mutations in human PS1 and PS2 homologs are a cause of familial Alzheimer's disease (AD). The function of the recently identified ancient family of IMPAS proteins (IMP/SPP/PSH) homologous to PSs is not yet known. We show here that, unlike PSs, IMPs (orthologous C. elegans Ce-imp-2 and human hIMP1/SPP) do not promote Notch (C. elegans lin-12,glp-1) proteolysis or signaling. The knock-down of Ce-imp-2 leads to embryonic death and an abnormal molting phenotype in Caenorhabditis elegans. The molting defect induced by Ce-imp-2 deficiency was mimicked by depleting cholesterol or disrupting Ce-lrp-1 and suppressed, in part, by expression of the Ce-lrp-1 derivate. C. elegans lrp-1 is a homolog of mammalian megalin, lipoprotein receptor-related protein (LRP) receptors essential for cholesterol and lipoprotein endocytosis and signaling. These data suggest that IMPs are functionally distinct from related PSs and implicate IMPs as critical regulators of development that may potentially interact with the lipid-lipoprotein receptor-mediated pathway.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=15469912&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC522053/
dc.subjectAnimals
dc.subjectCaenorhabditis elegans
dc.subjectCaenorhabditis elegans Proteins
dc.subjectCloning, Molecular
dc.subjectEndopeptidases
dc.subjectGene Expression Regulation, Developmental
dc.subjectMembrane Proteins
dc.subjectRNA Interference
dc.subjectRNA, Double-Stranded
dc.subjectRecombinant Proteins
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume101
dc.source.issue41
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1759
dc.identifier.contextkey808524
html.description.abstract<p>Presenilins (PSs) are required for Notch signaling in the development of vertebrates and invertebrates. Mutations in human PS1 and PS2 homologs are a cause of familial Alzheimer's disease (AD). The function of the recently identified ancient family of IMPAS proteins (IMP/SPP/PSH) homologous to PSs is not yet known. We show here that, unlike PSs, IMPs (orthologous C. elegans Ce-imp-2 and human hIMP1/SPP) do not promote Notch (C. elegans lin-12,glp-1) proteolysis or signaling. The knock-down of Ce-imp-2 leads to embryonic death and an abnormal molting phenotype in Caenorhabditis elegans. The molting defect induced by Ce-imp-2 deficiency was mimicked by depleting cholesterol or disrupting Ce-lrp-1 and suppressed, in part, by expression of the Ce-lrp-1 derivate. C. elegans lrp-1 is a homolog of mammalian megalin, lipoprotein receptor-related protein (LRP) receptors essential for cholesterol and lipoprotein endocytosis and signaling. These data suggest that IMPs are functionally distinct from related PSs and implicate IMPs as critical regulators of development that may potentially interact with the lipid-lipoprotein receptor-mediated pathway.</p>
dc.identifier.submissionpathoapubs/1759
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentBrudnick Neuropsychiatric Research Institute, Department of Psychiatry
dc.source.pages14955-60


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