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

In sexually reproducing organisms, activation of fertilization-competent sperm requires 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. Strains with partial deletions of the IDR are fertile at low temperatures but sterile at elevated temperatures. Larger deletions of the IDR are infertile at low and high 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.