A novel testis-specific GTPase serves as a link to proteasome biogenesis: functional characterization of RhoS/RSA-14-44 in spermatogenesis.
Most Rho family GTPases serve as key molecular switches in a wide spectrum of biological processes. An increasing number of studies have expanded their roles to the spermatogenesis. Several members of Rho family have been confirmed to be essential for mammalian spermatogenesis, but the precise roles of this family in male reproduction have not been well studied yet. Here we report a surprising function of an atypical and testis-specific Rho GTPase, RSA-14-44 in spermatogenesis. Featured by unique structural and expressional patterns, RSA-14-44 is distinguished from three canonical members of Rho cluster. Thus, we define RSA-14-44 as a new member of Rho GTPases family and rename it RhoS (Rho in spermatogenic cells). RhoS associates with PSMB5, a catalytic subunit of the proteasome, in a series of stage-specific spermatogenic cells. More importantly, RhoS does not directly modulate the cellular proteasome activity, but participates in regulating the stability of "unincorporated" PSMB5 precursors. Meanwhile, our data demonstrate that the activation of RhoS is prerequisite for negatively regulating the stability of PSMB5 precursors. Therefore, our finding uncovers a direct and functional connection between the Rho GTPase family and the pathway of proteasome biogenesis and provide new clues for deciphering the secrets of spermatogenesis.
Zhang
Ning
N
Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing, China.
Liang
Junbo
J
Tian
Yongqiang
Y
Yuan
Ligang
L
Wu
Lan
L
Miao
Shiying
S
Zong
Shudong
S
Wang
Linfang
L
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D046988:Proteasome Endopeptidase Complex; C478803:Psmb5 protein, rat; D020741:rho GTP-Binding Proteins