HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling

HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling

Xiajun Li* and
Iva Greenwald*,†,‡,§

^*Integrated Program in Cellular, Molecular and Biophysical Studies, ^†Department of Biochemistry and Molecular Biophysics, and ^‡Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032

Communicated by Thomas W. Cline, University of California, Berkeley, CA (received for review August 8, 1997)

Abstract

Mutant presenilins have been found to cause Alzheimer disease. Here, we describe the identification and characterization of HOP-1, a Caenorhabditis elegans presenilin that displays much more lower sequence identity with human presenilins than does the other C. elegans presenilin, SEL-12. Despite considerable divergence, HOP-1 appears to be a bona fide presenilin, because HOP-1 can rescue the egg-laying defect caused by mutations in sel-12 when hop-1 is expressed under the control of sel-12 regulatory sequences. HOP-1 also has the essential topological characteristics of the other presenilins. Reducing hop-1 activity in a sel-12 mutant background causes synthetic lethality and terminal phenotypes associated with reducing the function of the C. elegans lin-12 and glp-1 genes. These observations suggest that hop-1 is functionally redundant with sel-12 and underscore the intimate connection between presenilin activity and LIN-12/Notch activity inferred from genetic studies in C. elegans and mammals.

Footnotes

↵ § To whom reprint requests should be addressed at: Department of Biochemistry and Molecular Biophysics, 701 West 168th Street, Room 720, New York, NY 10032. e-mail: greenwald{at}cuccfa.ccc.columbia.edu.
ABBREVIATIONS:

PS1,

presenilin 1;

PS2,

presenelin 2;

Egl,

egg-laying defective;

RACE,

rapid amplification of cDNA ends