The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans

In sexually reproducing organisms, fertilization-competent sperm require activation via acrosomal vesicle exocytosis. We characterized the C. elegans gene spe-56, which encodes a single-pass transmembrane protein containing a C-terminal intrinsically disordered region (IDR). SPE-56 localizes to acrosomal-like membranous organelles (MOs) in the sperm, and loss of spe-56 causes sterility due to defective MO–plasma membrane fusion during sperm activation. Genetic epistasis places SPE-56 downstream of the canonical SPE-8/SPE-6 sperm activation pathway, which comprises a membrane receptor and a kinase. Sequential deletions within the IDR generate temperature-sensitive alleles that are fertile at low temperatures but sterile at elevated temperatures. These data indicate that SPE-56 promotes acrosomal-like exocytosis and that its IDR contributes to the thermal robustness of sperm activation. Overall, IDR-mediated structural flexibility may represent a conserved mechanism for maintaining sperm function across variable temperatures.