CGC Bibliography Paper 3110

Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins.

Li X, Greenwald I

Medline:

98284066

Citation:

Proceedings of the National Academy of Sciences USA 95: 7109-7114 1998

Type:

ARTICLE

Genes:

lin-12 sel-12

Abstract:

Presenilins have been implicated in the genesis of Alzheimer's disease and in facilitating LIN-12/Notch activity during development. All presenilins have multiple hydrophobic regions that could theoretically span a membrane, and a description of the membrane topology is a crucial step toward deducing the mechanism of presenilin function. Previously we proposed an eight-transmembrane-domain model for presenilin, based on studies of the Caenorhabditis elegans SEL-12 presenilin. Here, we describe experiments that support the view that two of the hydrophobic regions of SEL-12 function as the seventh and eighth transmembrane domains. Furthermore, we have shown that human presenilin 1 behaves like SEL-12 presenilin when analyzed by our methods. Our results provide additional experimental support for the eight-transmembrane-domain model of presenilin topology.