The murine septin4 gene (Sept4) has been implicated in diverse cellular functions, including cytokinesis, apoptosis, and tumor suppression. Here, we investigated the function of Sept4 proteins during mouse development by creating a targeted deletion of the Sept4 genomic locus. Sept4 mutant mice are viable but male sterile due to immotile and structurally defective sperm. During spermatogenesis, Sept4 proteins were essential for proper mitochondrial architecture and establishment of the annulus, a ring-like structure in the tail region of sperm. In addition, Sept4 mutant sperm showed defects in the elimination of residual cytoplasm during sperm maturation and had increased staining for the caspase inhibitor XIAP. This is consistent with a role of the proapoptotic Sept4 protein ARTS in promoting caspase-mediated removal of cytoplasm via inhibition of XIAP. Our results indicate that Sept4 proteins play distinct but evolutionarily conserved functions in different cellular compartments.
Bibliographical noteFunding Information:
We would like to thank Eli Arama, Mathew Hardy, and David Phillips for helpful suggestions and critical reading of the manuscript and Helen Shio at the EM facility at the Rockefeller University for her excellent skills. We are grateful to the Gene Expression Nervous System Atlas (GENSAT) project and to the National Institute of Neurological Disorders and Stroke Contract N01NS02331 to The Rockefeller University (New York, NY) for providing us with the BAC Septin4-EGFP transgenic line. H.S. is an Investigator of the Howard Hughes Medical Institute. Part of this work was supported by a Fogarty International Research Collaboration Award grant from the National Institute of Health and a Focused Giving Award from Johnson & Johnson to H.S. G.R.H. is supported in part by National Institutes of Health grant R01-HD38807.
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology (all)
- Developmental Biology
- Cell Biology