Speriolin is a novel spermatogenic cell-specific centrosomal protein associated with the seventh WD motif of Cdc20.
The fundamental mechanisms of mitosis are conserved throughout evolution in eukaryotes, including ubiquitin-mediated proteolysis of cell cycle regulators by the anaphase-promoting complex/cyclosome. The spindle checkpoint protein Cdc20 activates the anaphase-promoting complex/cyclosome in a substrate-specific manner. It is present in the cytoplasm and concentrated in the centrosomes throughout the cell cycle, accumulates at the kinetochores in metaphase, and is no longer detected following anaphase. However, it is unknown whether Cdc20 has the same activities and distribution during meiosis in male germ cells. We found that in mice, Cdc20 accumulates in the cytoplasm of pachytene spermatocytes during meiosis I, is distributed throughout spermatocytes undergoing meiotic division, and is present in the cytoplasm of postmeiotic spermatids. Several proteins bind to and regulate the function of Cdc20 during mitosis. We identified speriolin and determined that it is a novel spermatogenic cell-specific Cdc20-binding protein, is present in the cytoplasm, and is concentrated at the centrosomes of spermatocytes and spermatids and that a leucine zipper domain is required to target speriolin to the centrosome. The seven tandem WD motifs of Cdc20 probably fold into a seven-blade beta-propeller structure, and we determined that they are required for speriolin binding and for localization of Cdc20 to the centrosomes and nucleus, suggesting that speriolin might regulate or stabilize the folding of Cdc20 during meiosis in spermatogenic cells.
Goto
Masuo
M
Gamete Biology Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Eddy
Edward M
EM
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002458:Cell Fractionation; D018385:Centrosome / Q000737:chemistry*; D003001:Cloning, Molecular; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D013091:Spermatogenesis; D013737:Testis / Q000737:chemistry / Q000166:cytology; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C492988:Spatc1 protein, mouse