The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins

Anastasia P. Grigorenko, Yuri K. Moliaka, Martha Soto, Craig C. Mello, Evgeny I. Rogaev

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

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-Irp-1 and suppressed, in part, by expression of the Ce-Irp-1 derivate. C elegans Irp-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.

Original languageEnglish (US)
Pages (from-to)14955-14960
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number41
DOIs
StatePublished - Oct 12 2004

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'The Caenorhabditis elegans IMPAS gene, imp-2, is essential for development and is functionally distinct from related presenilins'. Together they form a unique fingerprint.

  • Cite this