Identification and characterization of a novel Rab GTPase-activating protein in spermatids.
We have previously identified novel testis-specific genes by microarray analysis of human testicular tissues. One of the novel genes is Male Germ Cells Rab GTPase- Activating Proteins (MgcRabGAP), which is characterized by the conserved RabGAP catalytic domain, TBC (Tre2/Bub2/Cdc16). RabGAPs are involved in various physiological processes (e.g. vesicular trafficking, cytoskeletal remodelling, cell migration, etc.) by inactivating Rab proteins. In this study, we found that MgcRabGAP transcripts are mainly expressed in the mouse and human testes. The MgcRabGAP protein is expressed in the elongating and elongated spermatids. Immunofluorescence assay of mouse germ cells showed that the protein expression is enriched at the edge of the acrosomal region, neck and annulus during spermiogenesis. This MgcRabGAP is co-localized with its candidate substrate Rab3A at the acrosome/acroplaxome and neck regions of spermatids. Meanwhile, MgcRabGAP is co-localized and interacts with β-actin. In humans, the expression of MgcRabGAP is enriched at the stage of elongating spermatids. The amount of MGCRABGAP transcript is reduced in the testicular tissues of men with various types of spermatogenic defects. Considering that MGCRABGAP is exclusively expressed in post-meiotic male germ cells, the decreased transcript amount may be a phenomenon secondary to loss of germ cells in the testicular samples. Our finding strongly suggests that MgcRabGAP is involved in acrosome/acroplaxome formation and cytoskeletal reorganization via Rab activity during mammalian spermiogenesis.
Graduate Institute of Basic Medical Sciences Department of Urology Institute of Molecular Medicine Department of Obstetrics & Gynecology, National Cheng Kung University, College of Medicine, Tainan, Taiwan.
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Lin
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Lin
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Kuo
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Wang
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Kuo
D000177:Acrosome / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D003599:Cytoskeleton / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007248:Infertility, Male / Q000503:physiopathology; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013087:Spermatids / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D008840:Microfilament Proteins; C000602436:TBC1D21 protein, human; C569405:Tbc1d21 protein, mouse; C115995:mgcRacGAP; D020826:rab3A GTP-Binding Protein