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.
Zhou
Jing
J
The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Du
Ya-Rui
YR
Qin
Wei-Hua
WH
Hu
Ye-Guang
YG
Huang
Yan-Nv
YN
Bao
Lan
L
Han
Daishu
D
Mansouri
Ahmed
A
Xu
Guo-Liang
GL
D000177:Acrosome / Q000502:physiology / Q000648:ultrastructure; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D007248:Infertility, Male / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology*; D009154:Mutation; D013077:Sperm Head / Q000502:physiology / Q000648:ultrastructure; D013087:Spermatids / Q000502:physiology* / Q000648:ultrastructure; D013091:Spermatogenesis / Q000502:physiology*
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C471056:Hook1 protein, mouse; D008869:Microtubule-Associated Proteins; C540452:RIM-BP3 protein, mouse