RIM-BP3 is a manchette-associated protein essential for spermiogenesis

During spermiogenesis, round spermatids are converted into motile sperm in mammals. The mechanisms responsible for sperm morphogenesis are poorly understood. We have characterized a novel protein, RIM-BP3, with a specialized function in spermatid development in mice. The RIM-BP3 protein is associated with the manchette, a transient microtubular structure believed to be important for morphogenesis during spermiogenesis. Targeted deletion of the RIM-BP3 gene resulted in male infertility owing to abnormal sperm heads, which are characterized by a deformed nucleus and a detached acrosome. Consistent with its role in morphogenesis, the RIM-BP3 protein physically associates with Hook1, a known manchette-bound protein required for sperm head morphogenesis. Interestingly, RIM-BP3 does not interact with the truncated Hook1 protein characterized in azh (abnormal spermatozoon head) mutant mice. Moreover, RIM-BP3 and Hook1 mutant mice display several common abnormalities, in particular with regard to the ectopic positioning of the manchette within the spermatid, a presumed cause of sperm head deformities. These observations suggest an essential role for RIM-BP3 in manchette development and function through its interaction with Hook1. As the occurrence of deformed spermatids is one of the common abnormalities leading to malfunctional sperm, identification of RIM-BP3 might provide insight into the molecular cue underlying causes of male infertility in humans.