Actin-related protein M1 (ARPM1) required for acrosome biogenesis and sperm function in mice

Actin-related proteins (Arps) are a superfamily of proteins which share sequence similarities with conventional actin and are involved in different cellular processes. Actin-related protein M1 (ARPM1) also known as actin-related protein T3 (ACTRT3) is a testis-enriched Arp which can be found in the perinuclear theca (PT) of murine round and elongating spermatids. ARPM1 forming a complex with Profilin 3 (PFN3) is lost in Pfn3-deficient sperm. We generated a mouse model deficient for Arpm1 and demonstrate that Arpm1-/- male mice are subfertile, with morphological aberrations of the acrosome. During spermiogenesis, defects become apparent in Cap phase of acrosome biogenesis when abnormal acrosomal granules are observed. Arpm1-deficiency causes deregulation of GM130 and TGN46 suggestive of defects in cis- and trans-Golgi trafficking required for acrosome development. Co-immunoprecipitation revealed that ARPM1 interacts with the PT-specific proteins ACTRT1, ACTRT2, ACTL7A and the sperm surface protein ZPBP, additionally to its already shown interaction with PFN3. We propose that ARPM1 acts as a structural component of the PT contributing to the cytoskeletal network connecting acrosome and nucleus. In addition, ARPM1 mediates the localization of ZPBP to enable fertilization and it tethers PFN3 to properly regulate Golgi-related acrosome development.