Summary Motility of sperm is crucial for their directed migration to the egg. The acquisition and modulation of motility are regulated to ensure that sperm move when and where needed, thereby promoting reproductive success. One specific example of this phenomenon occurs during differentiation of the amoeboid sperm of C. elegans as they activate from a round spermatid to a mature, crawling spermatozoon. Sperm activation is regulated by redundant pathways to occur at a specific time and place for each sex. Here, we report the identification of the solute carrier 6 (SLC6) transporter protein SNF-10 as a key regulator of C. elegans sperm activation in response to male protease activation signals. We find that SNF-10 is present in sperm and is required for activation by the male but not by the hermaphrodite. Loss of both snf-10 and a hermaphrodite activation factor render sperm completely insensitive to activation. Using in vitro assays, we find that snf-10 mutant sperm show a specific deficit in response to protease treatment but not to other activators. Prior to activation, SNF-10 is present in the plasma membrane, where it represents a strong candidate to receive signals that lead to subcellular morphogenesis. After activation, it shows polarized localization to the cell body region that is dependent on membrane fusions mediated by the dysferlin FER-1. Our discovery of snf-10 offers insight into the mechanisms differentially employed by the two sexes to accomplish the common goal of producing functional sperm, as well as how the physiology of nematode sperm may be regulated to control motility as it is in mammals.

Sperm from the nematode C. elegans gain motility during a process termed activation, which they initiate in response to specific environmental signals. During this process, a number of subcellular rearrangements occur, culminating in an altered morphology that allows the cell to crawl toward and fertilize oocytes. Both hermaphrodites and males produce sperm, and redundant, sex-biased pathways regulate the sperm's activation. The male-derived signal for sperm activation involves TRY-5, a trypsin-like serine protease in seminal fluid, but until recently it was unknown what factors were active downstream of TRY-5. In our recent paper, we reported the discovery of SNF-10, a solute carrier 6 (SLC6) family protein that is expressed by sperm and connects the activation signal to changes in sperm morphology and, ultimately, the onset of motility. Here, we review our recent results, focusing on potential models for SNF-10's function in C. elegans, and additionally discuss the role SLC6 transporters may play in male reproductive biology from invertebrates to mammals.