Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice.
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 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 IFT-B complex, and IFT140, a component of 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.
Department of Gastroenterology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430030 Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
Zhengang
Z
Zhang
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
Wei
W
Li
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 Department of Dermatology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430030.
Yong
Y
Zhang
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065.
Ling
L
Zhang
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
Maria E
ME
Teves
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065.
Hong
H
Liu
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298.
Jerome F
JF
Strauss
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
Gregory J
GJ
Pazour
Department of Biology, Randolph-Macon College, Ashland, VA 23005.
James A
JA
Foster
Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln, Urbana, IL 61802-6199.
Rex A
RA
Hess
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, 23298 zhibing.zhang@vcuhealth.org.
Zhibing
Z
Zhang
Anat Rec. 1979 Jun;194(2):233-46
464324
Chromosoma. 2003 May;111(8):483-8
12743712
J Biol Chem. 2003 Sep 5;278(36):34211-8
12821668
Biol Reprod. 2004 Sep;71(3):1016-25
15163613
Cell. 2004 May 14;117(4):527-39
15137945
Curr Top Dev Biol. 2008;85:23-61
19147001
Dev Biol. 2009 Nov 1;335(1):166-78
19732765
Am J Anat. 1987 Jan;178(1):72-80
3825964
Methods Mol Biol. 2016;1454:69-82
27514916
Mol Biol Cell. 2011 Apr;22(7):921-30
21307337
Nat Genet. 1999 Sep;23(1):118-21
10471512
Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):165-74
22791528
Autophagy. 2015;11(5):847-9
25945523
Front Biosci. 2008 Jan 01;13:2633-52
17981739
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11325-30
16061793
J Cell Sci. 2014 May 1;127(Pt 9):1924-37
24554435
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17055-60
19805151
Biol Reprod. 2010 Mar;82(3):580-90
19889948
Tissue Cell. 1987;19(4):479-93
3498237
Genesis. 2008 Dec;46(12):738-42
18850594
Genesis. 2013 Jul;51(7):481-90
23554062
Development. 2000 Jun;127(11):2347-55
10804177
Nat Genet. 2001 May;28(1):82-6
11326282
Cell. 2016 Aug 11;166(4):797-9
27518558
Biol Reprod. 2003 Jul;69(1):211-7
12620939
Nat Cell Biol. 2009 Nov;11(11):1332-9
19855387
Mol Biol Cell. 2015 Dec 1;26(24):4358-72
26424803
PLoS Genet. 2008 Dec;4(12):e1000315
19112494
Cell Res. 2014 Jul;24(7):852-69
24853953
Mol Reprod Dev. 2002 Sep;63(1):1-4
12211054
Development. 2015 Mar 1;142(5):921-30
25715396
J Cell Biol. 2008 Nov 3;183(3):377-84
18981227
Andrology. 2013 Jan;1(1):37-46
23258628
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6852-7
17426145
Biol Reprod. 2009 Jan;80(1):162-74
18799754
Curr Biol. 2003 Sep 30;13(19):1679-86
14521833
Bone Res. 2014 Nov 18;2:14038
26097753
Mol Cell Biol. 2001 Nov;21(21):7243-55
11585907
J Biol Chem. 2005 Jul 29;280(30):27688-96
15955805
Dev Biol. 2009 Jan 1;325(1):225-37
19000668
Nat Genet. 2008 Apr;40(4):403-10
18327258
FASEB J. 2015 Oct;29(10 ):4145-61
26183773
Scanning Microsc. 1987 Sep;1(3):1249-55
3498985
Med Sci (Paris). 2014 Nov;30(11):955-61
25388576
Cell Motil Cytoskeleton. 2009 Aug;66(8):457-68
19253336
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5987-92
23530209
Curr Biol. 2003 Sep 30;13(19):1687-96
14521834
EMBO J. 2016 Apr 1;35(7):773-90
26912722
Sci Rep. 2016 Jan 04;6:18278
26726850
Mol Biol Cell. 2006 Sep;17(9):3781-92
16775004
Annu Rev Genomics Hum Genet. 2006;7:125-48
16722803
J Anim Breed Genet. 2012 Apr;129(2):92-7
22394230
Reproduction. 2012 Mar;143(3):347-57
22157319
Mol Hum Reprod. 1999 Mar;5(3):206-13
10333353
J Cell Sci. 2012 Oct 15;125(Pt 20):4740-50
22797916
Bioscience. 2014 Dec 1;64(12):1126-1137
25960570
Reproduction. 2016 Apr;151(4):R43-54
26792866
Mol Cell. 2009 May 15;34(3):259-69
19450525
Biol Reprod. 2011 Oct;85(4):690-701
21715716
Biol Pharm Bull. 2015;38(8):1098-103
26235572
Development. 2015 Feb 1;142(3):555-66
25605782
Semin Cell Dev Biol. 2014 Jun;30:55-64
24280271
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5043-8
10220415
Cell. 1998 Dec 11;95(6):829-37
9865700
Nat Genet. 2000 Aug;25(4):448-52
10932193
Biol Reprod. 2004 Oct;71(4):1220-9
15189834
Int J Biochem Cell Biol. 2004 Dec;36(12):2503-18
15325588
Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5519-23
8516294
Biol Reprod. 2004 Aug;71(2):548-59
15084482
Hum Mol Genet. 2011 Oct 1;20(19):3725-37
21653639
J Mol Biol. 2012 Sep 14;422(2):163-80
22683354
Nature. 2013 Oct 10;502(7470):194-200
24089209
Mol Cell Biol. 2005 Aug;25(16):7107-19
16055721
N Engl J Med. 2011 Apr 21;364(16):1533-43
21506742
Nature. 2015 Apr 23;520(7548):563-6
25686604
Trends Biochem Sci. 2015 Dec;40(12 ):765-78
26498262
Biol Reprod. 2006 Apr;74(4):751-9
16382026