Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of Acrbp in the mouse.
Proper biogenesis of a sperm-specific organelle, the acrosome, is essential for gamete interaction. An acrosomal matrix protein, ACRBP, is known as a proacrosin-binding protein. In mice, two forms of ACRBP, wild-type ACRBP-W and variant ACRBP-V5, are generated by pre-mRNA alternative splicing of Acrbp Here, we demonstrate the functional roles of these two ACRBP proteins. ACRBP-null male mice lacking both proteins showed a severely reduced fertility, because of malformation of the acrosome. Notably, ACRBP-null spermatids failed to form a large acrosomal granule, leading to the fragmented structure of the acrosome. The acrosome malformation was rescued by transgenic expression of ACRBP-V5 in ACRBP-null spermatids. Moreover, exogenously expressed ACRBP-W blocked autoactivation of proacrosin in the acrosome. Thus, ACRBP-V5 functions in the formation and configuration of the acrosomal granule during early spermiogenesis. The major function of ACRBP-W is to retain the inactive status of proacrosin in the acrosome until acrosomal exocytosis.
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Yoshinori
Y
Kanemori
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Yoshitaka
Y
Koga
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Mai
M
Sudo
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Woojin
W
Kang
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Shin-Ichi
S
Kashiwabara
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan;
Masahito
M
Ikawa
Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan;
Hidetoshi
H
Hasuwa
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Kiyoshi
K
Nagashima
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan;
Yu
Y
Ishikawa
RIKEN BioResource Center, Tsukuba Science City, Ibaraki 305-0074, Japan;
Narumi
N
Ogonuki
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; RIKEN BioResource Center, Tsukuba Science City, Ibaraki 305-0074, Japan;
Atsuo
A
Ogura
Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan; Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8577, Japan baba.tadashi.gf@u.tsukuba.ac.jp.
Tadashi
T
Baba
D000177:Acrosome / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D013091:Spermatogenesis; D013094:Spermatozoa / Q000254:growth & development / Q000378:metabolism*
C575070:ACRBP protein, mouse; D002352:Carrier Proteins; D020033:Protein Isoforms; D012322:RNA Precursors
acrosomal biogenesis; alternative splicing; fertilization; mouse; spermiogenesis