Dual functions of Intraflagellar Transport Protein IFT20 in spermiogenesis: formation of sperm flagella and removal of cytoplasm by autophagy

Intraflagellar transport (IFT) is a conserved mechanism thought to be essential for the assembly and maintenance of cilia and flagella. However, little is known about mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile with significantly reduced sperm counts and motility. In addition, abnormally shaped elongating spermatid heads and bulbous round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria and decreased mature lysosomes. The few developed sperm had disrupted axoneme and retained cytoplasmic lobe components on the flagella. ODF2 and SPAG16L, two sperm flagella proteins failed to be incorporated into sperm tails of the mutant mice. Expression levels of an autophagy core protein that associates with IFT20, Atg16, were significantly reduced in the testis of the Ift20 mutant mice. Our studies suggest that IFT20 is essential for spermiogenesis in mice, and it plays a role in sperm flagella formation, and removing excess cytoplasmic components by regulating autophagy core proteins.