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Dev Cell. 2012 Jul 17;23(1):82-96. doi: 10.1016/j.devcel.2012.04.021.

Hibris, a Drosophila nephrin homolog, is required for presenilin-mediated Notch and APP-like cleavages.

Author information

1
Department of Developmental & Regenerative Biology, Mount Sinai School of Medicine and Graduate School of Biological Sciences, One Gustave L. Levy Place, New York, NY 10029, USA.

Abstract

Drosophila Hibris (Hbs), a member of the Nephrin Immunoglobulin Super Family, has been implicated in myogenesis and eye patterning. Here, we uncover a role of Hbs in Notch (N) signaling and γ-secretase processing. Loss of hbs results in classical N-signaling-associated phenotypes in Drosophila, including eye patterning, wing margin, and sensory organ specification defects. In particular, hbs mutant larvae display altered γ-secretase-dependent Notch proteolytic processing. Hbs also interacts molecularly and genetically with Presenilin (Psn) and other components of the γ-secretase complex. This Hbs function appears conserved, as mammalian Nephrin also promotes N signaling in mammalian cells. Our data suggest that Hbs is required for Psn maturation. Consistent with its role in Psn processing, Hbs genetically interacts with the Drosophila β-amyloid protein precursor-like (Appl) protein, the homolog of mammalian APP, the cleavage of which is associated with Alzheimer's disease. Thus, Hbs/Nephrin appear to share a general requirement in Psn/γ-secretase regulation and associated processes.

PMID:
22814602
PMCID:
PMC3475182
DOI:
10.1016/j.devcel.2012.04.021
[Indexed for MEDLINE]
Free PMC Article

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