A novel function for the presenilin family member spe-4: inhibition of spermatid activation in Caenorhabditis elegans.

BACKGROUND: Sperm cells must regulate the timing and location of activation to maximize the likelihood of fertilization. Sperm from most species, including the nematode Caenorhabditis elegans, activate upon encountering an external signal. Activation for C. elegans sperm occurs as spermatids undergo spermiogenesis, a profound cellular reorganization that produces a pseudopod. Spermiogenesis is initiated by an activation signal that is transduced through a series of gene products. It is now clear that an inhibitory pathway also operates in spermatids, preventing their premature progression to spermatozoa and resulting in fine-scale control over the timing of activation. Here, we describe the involvement of a newly assigned member of the inhibitory pathway: spe-4, a homolog of the human presenilin gene PS1. The spe-4(hc196) allele investigated here was isolated as a suppressor of sterility of mutations in the spermiogenesis signal transduction gene spe-27. RESULTS: Through mapping, complementation tests, DNA sequencing, and transformation rescue, we determined that allele hc196 is a mutation in the spe-4 gene. Our data show that spe-4(hc196) is a bypass suppressor that eliminates the need for the spermiogenesis signal transduction. On its own, spe-4(hc196) has a recessive, temperature sensitive spermatogenesis-defective phenotype, with mutants exhibiting (i) defective spermatocytes, (ii) defective spermatids, (iii) premature spermatid activation, and (iv) spermatozoa defective in fertilization, in addition to a small number of functional sperm which appear normal microscopically. CONCLUSION: A fraction of the sperm from spe-4(hc196) mutant males progress directly to functional spermatozoa without the need for an activation signal, suggesting that spe-4 plays a role in preventing spermatid activation. Another fraction of spermatozoa from spe-4(hc196) mutants are defective in fertilization. Therefore, prematurely activated spermatozoa may have several defects: we show that they may be defective in fertilization, and earlier work showed that they obstruct sperm transfer from males at mating. hc196 is a hypomorphic allele of spe-4, and its newly-discovered role inhibiting spermiogenesis may involve known proteolytic and/or calcium regulatory aspects of presenilin function, or it may involve yet-to-be discovered functions.