TY - JOUR
T1 - Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice
AU - Li, Wei
AU - Zhang, Yong
AU - Zhang, Ling
AU - Tevesb, Maria E.
AU - Liu, Hong
AU - Strauss, Jerome F.
AU - Pazour, Gregory J.
AU - Foster, James A.
AU - Hess, Rex A.
AU - Zhang, Zhibing
AU - Zhang, Zhengang
N1 - Funding Information:
This research was supported by National Institutes of Health Grant HD076257, the Virginia Commonwealth University Presidential Research Incentive Program and a Massey Cancer Award (to Z.Z.), National Institutes of Health Grant GM060992 (to G.J.P.), Chenery and Rashkind Grants from Randolph-Macon College (to J.F.), Youth Talents of Health and Family Planning Commission of Hubei Province of China (WJ2015Q026), and the National Natural Science Foundation of China (81571428, 81502792, 81300536, 81172462, and 81671514). Confocal microscopy and SEM were performed in the VCU Microscopy Facility of Virginia Commonwealth University (5P30NS047463). TEM was performed at Randolph-Macon College by Courtney Stevens and Brandon Delpi (NSF1229184).
PY - 2016/11/15
Y1 - 2016/11/15
N2 - Intraflagellar transport (IFT) is a conserved mechanism believed to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in 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 a decrease in mature lysosomes. The few developed sperm had disrupted axonemes, and some 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, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of the IFT-B complex, and IFT140, a component of the IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin, were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components.
AB - Intraflagellar transport (IFT) is a conserved mechanism believed to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in 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 a decrease in mature lysosomes. The few developed sperm had disrupted axonemes, and some 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, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of the IFT-B complex, and IFT140, a component of the IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin, were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components.
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U2 - 10.1091/mbc.E16-05-0318
DO - 10.1091/mbc.E16-05-0318
M3 - Article
AN - SCOPUS:84995750540
SN - 1059-1524
VL - 27
SP - 3705
EP - 3716
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 23
ER -