SPIN-4/Spinster supports sperm activation in C. elegans via sphingosine-1-phosphate transport

Spermiogenesis, a sperm-activation step, is crucial for the transformation of immotile spermatids into motile sperm. Though membrane transport of ions and molecules across the sperm plasma membrane has been implicated in this process, the full repertoire of transporters involved, and their respective substrates, is unclear. Here, we report that the major facilitator superfamily transporter SPIN-4/Spinster governs efficient spermiogenesis and fertility in the hermaphrodite nematode Caenorhabditis elegans. Unlike other C. elegans Spinster paralogs, SPIN-4 is germline-expressed. Moreover, SPIN-4 expression is gamete-specific; it is strongly expressed in developing sperm, where it localizes to the plasma membrane, but it is absent from oocytes. Consistent with these expression data, we demonstrate that knocking out spin-4 impairs sperm development, leading to the formation of non-motile sperm that lack pseudopodia. Consequently, hermaphrodites homozygous for the spin-4 (knu1099) knockout allele show extensive sperm wasting and reduced self-progeny. We observe similar defects when we genetically inhibit production of sphingosine-1-phosphate, a lipid molecule that stimulates cell motility when exported extracellularly by Spinster homologs in other contexts. Remarkably, extracellular supplementation with sphingosine-1-phosphate rescues sperm activation and motility in the absence of SPIN-4, suggesting that Spinster-dependent efflux of sphingosine-1-phosphate plays a key role in sperm mobilization. These findings identify a new signaling mechanism in C. elegans spermiogenesis entailing Spinster and sphingosine-1-phosphate.