LASP1, a Novel Protein in Spermatozoa and Acrosome Reaction

LIM and SH3 protein 1 (LASP1) is a widely expressed scaffold protein associated with actin-rich structures. In Lasp1-knockout mice, reproductive defects such as longer intervals between litters and reduced pup numbers were observed. Consistently, data from the Human Protein Atlas show strong LASP1 expression in spermatids, suggesting a reproductive role. Mammalian fertilization involves sequential processes of sperm activation, capacitation, and acrosome reaction, driven by bicarbonate-mediated PKA activation, CNP-regulated PKG stimulation, F-actin polymerization, Ca²⁺-signaling, and MAPK signaling pathways - culminating in membrane fusion and CD44 cluster formation for interaction with the egg. In this context, we observed differential isoform expression of PKG in human and mice. Our data provide the first evidence of LASP1 presence in the head, midpiece, and tail of human and mouse spermatozoa. During capacitation, LASP1 undergoes dynamic changes, co-localizes with F-actin and stabilizes the equatorial ring segment. In mice, loss of LASP1 did not affect sperm morphology, motility or chemotaxis, but led to changes in protein phosphorylation, incomplete capacitation, and reduced hyaluronan receptor surface expression, revealing a novel role of LASP1 in sperm fertilization.