The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins
UMass Chan Affiliations
Program in Molecular MedicineBrudnick Neuropsychiatric Research Institute, Department of Psychiatry
Document Type
Journal ArticlePublication Date
2004-10-08Keywords
AnimalsCaenorhabditis elegans
Caenorhabditis elegans Proteins
Cloning, Molecular
Endopeptidases
Gene Expression Regulation, Developmental
Membrane Proteins
RNA Interference
RNA, Double-Stranded
Recombinant Proteins
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14955-60. Epub 2004 Oct 6. Link to article on publisher's site
DOI
10.1073/pnas.0406462101Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38927PubMed ID
15469912Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0406462101