Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1.
Presenilins are part of a protease complex that is responsible for the intramembraneous cleavage of the amyloid precursor protein involved in Alzheimer's disease and of Notch receptors. In Caenorhabditis elegans, mutations in the presenilin sel-12 result in a highly penetrant egg-laying defect. spr-5 was identified as an extragenic suppressor of the sel-12 mutant phenotype. The SPR-5 protein has similarity to the human polyamine oxidase-like protein encoded by KIAA0601 that is part of the HDAC-CoREST co-repressor complex. Suppression of sel-12 by spr-5 requires the activity of HOP-1, the second somatic presenilin in C.elegans. spr-5 mutants derepress hop-1 expression 20- to 30-fold in the early larval stages when hop-1 normally is almost undetectable. SPR-1, a C.elegans homologue of CoREST, physically interacts with SPR-5. Moreover, down-regulation of SPR-1 by mutation or RNA interference also bypasses the need for sel-12. These data strongly suggest that SPR-5 and SPR-1 are part of a CoREST-like co-repressor complex in C.elegans. This complex might be recruited to the hop-1 locus controlling its expression during development.
Eimer
S
S
ABI, Department of Biochemistry, Laboratory of Molecular Neurogenetics, Ludwig-Maximilians-Universität Munich, Schillerstrasse 44, Germany.
Lakowski
B
B
Donhauser
R
R
Baumeister
R
R
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D015536:Down-Regulation; D017353:Gene Deletion; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010089:Oxidoreductases, N-Demethylating; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C109040:Hop-1 protein, C elegans; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch; C095907:SEL-12 protein, C elegans; D010089:Oxidoreductases, N-Demethylating; C468848:SPR-5 protein, C elegans