Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1

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Abstract
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.