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Medientyp:
E-Artikel
Titel:
Effects of SEL-12 presenilin on LIN-12 localization and function in Caenorhabditis elegans
Beteiligte:
Levitan, Diane;
Greenwald, Iva
Erschienen:
The Company of Biologists, 1998
Erschienen in:
Development, 125 (1998) 18, Seite 3599-3606
Sprache:
Englisch
DOI:
10.1242/dev.125.18.3599
ISSN:
0950-1991;
1477-9129
Entstehung:
Anmerkungen:
Beschreibung:
ABSTRACT Presenilins have been implicated in the development of Alzheimer’s disease and in facilitating LIN-12/Notch activity. Here, we use genetic methods to explore the relationship between C. elegans LIN-12 and SEL-12 presenilin. Reducing sel-12 activity can suppress the effects of elevated lin-12 activity when LIN-12 is activated by missense mutations but not when LIN-12 is activated by removal of the extracellular and transmembrane domains. These results suggest that SEL-12 does not function downstream of activated LIN-12. An active SEL-12::GFP hybrid protein accumulates in the perinuclear region of the vulval precursor cells (VPCs) of living hermaphrodites, consistent with a localization in endoplasmic reticulum/Golgi membranes; when sel-12 activity is reduced, less LIN-12 protein accumulates in the plasma membranes of the VPCs. Together with the genetic interactions between lin-12 and sel-12, these observations suggest a role for SEL-12 in LIN-12 processing or trafficking. However, SEL-12 does not appear to be a general factor that influences membrane protein activity, since reducing sel-12 activity does not suppress or enhance hypomorphic mutations in other genes encoding membrane proteins. We discuss potential parallels for the role of SEL-12/presenilin in facilitating LIN-12/Notch activity and in amyloid precursor protein (APP) processing.