After their production, spermatids remain quiescent until they receive a signal to activate, stimulating a wholesale reorganization resulting in the crawling spermatozoon. Activation is signaled by the protease TRY-5 in males and by zinc in both hermaphrodites and males. Here we focus on zinc activation, which triggers a signal transduction pathway involving products of the spe-8 group genes (spe-8, spe-12, spe-19, spe-27, and spe-29). Mutations in any of the spe-8 group genes prevent spermiogenesis, and this group likely forms the receptor complex that interacts with extracellular zinc. SPE-12 and SPE-19 possess extracellular domains, and we have shown that SPE-8 (a tyrosine kinase) is localized to the membrane by other SPE-8 group members, but it moves to the interior during activation. A suppressor screen of spe-27(it132ts)I identified numerous mutations that restore fertility to spe-27 mutants. More than 20 suppressor mutations were recovered in spe-6. These spe-6 suppressors induce a partial loss of function, and most cause premature sperm activation. Thus, SPE-6 appears to inhibit spermatid activation. However, spe-6(zq11), is an allele specific suppressor that does not induce rampant premature activation, indicating that SPE-6 and SPE-27 interact physically. The remaining suppressor mutations all bypass the sperm activation signal with no two mutations affecting the same gene. One mutation affects spe-4, which encodes a Presenilin-1 homolog that localizes to the fibrous body-membranous organelle (FB-MO) membrane and is involved in loading MSP (major sperm protein) in the FB. Another mutation affected spe-47, whose product appears to associate with the FB-MO during its formation. SPE-47 is then degraded in secondary spermatocytes, long before spermatids are formed. A paralog of spe-47, Y48B6A.5, has a similar pattern of expression and may have redundant function with SPE-47. A fourth gene affected by a suppressor mutation is spe-46, whose role in spermatogenesis is unknown, but the suppressor mutation also causes a host of defects, in addition to premature sperm activation. Finally, a small gene, K01D12.7, also harbors a suppressor mutation. The function of K01D12.7 is unknown, but it resembles a signaling molecule. Our working hypothesis is that functional SPE-6 inhibits activation and interacts with SPE-27 during activation. Further, spermatids cannot refrain from activating when mutations cause errors in the formation of the FB-MO. Thus, both inhibition and properly formed FB-MOs are necessary to maintain the inactive spermatid.

Authors: De La Cruz, Aubrie, Christensen, Matthew, Huang, Haifen, Sokolich, Thomas, Prajapati, Gaurav, Clark, Jessica, Sullivan, Nicholas, LaMunyon, Craig

Affiliation:
- California State Polytech Univ, Pomona, CA