Identification and characterization of a novel Rab GTPase-activating protein in spermatids

Lin, Ying; Lin, Yung Ming; Kuo, Yung Che; Wang, Y. Y.; Kuo, Pao‐Lin

doi:10.1111/j.1365-2605.2010.01126.x

Cited by 24 publications

(37 citation statements)

References 48 publications

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“…Some proteins located at sperm annulus may be involved in regulating assembly/disassembly or stability of SEPT-related complex, including a novel Male Germ Cells Rab GTPase-Activating Proteins (MgcRabGAP), DNAJB13, a type 2 heart shock protein 40 (HSP40) and also a component of mouse sperm axoneme and TAT1, a new family member of Slc26 family of anion transporters. [38][39][40] Tat1 null males were sterile due to disorganization of the midpiece-principal piece junction and abnormal mitochondrial sheath assembly, a phenotype characteristic of SPET4 and SEPT12 deficiency. 40 It is also intriguing how SEPT12 deficiency results in nuclear DNA damage.…”

Section: Prospectsmentioning

confidence: 99%

The role of the septin family in spermiogenesis

et al. 2011

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Section: Prospectsmentioning

confidence: 99%

The role of the septin family in spermiogenesis

et al. 2011

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“…Human SEPT12 and NDC1 were amplified from a human RNA panel (Clontech, Mountain View, CA, USA) and cloned into pEGFP-N1 and pFLAG-CMV2 vectors, as described previously [33]. NT2D1 cells were transfected with the vectors through lipofection.…”

Section: Methodsmentioning

confidence: 99%

“…Overexpression of NDC1 or co-transfection with SEPT12 was replicated three times and more than 100 cells were counted per assay. The cells lysates and the antibodies (Anti-GFP antibody: sc-9996, Santa Cruz Biotechnology Inc.; anti-FLAG antibody: F1804, Sigma-Aldrich, St. Louis, MO, USA; Anti-NDC1 antibody: sc-161929, Santa Cruz Biotechnology Inc.) were used in the Co-IP and IB assays, by employing the procedure described in our previous study [33]. …”

Section: Methodsmentioning

confidence: 99%

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SEPT12–NDC1 Complexes Are Required for Mammalian Spermiogenesis

Lai

Wang

et al. 2016

IJMS

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Male factor infertility accounts for approximately 50 percent of infertile couples. The male factor-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile sperm, immature sperm, abnormally structured sperm, and sperm with nuclear damage. Our knockout and knock-in mice models demonstrated that SEPTIN12 (SEPT12) is vital for the formation of sperm morphological characteristics during spermiogenesis. In the clinical aspect, mutated SEPT12 in men results in oligozoospermia or teratozoospermia or both. Sperm with mutated SEPT12 revealed abnormal head and tail structures, decreased chromosomal condensation, and nuclear damage. Furthermore, several nuclear or nuclear membrane-related proteins have been identified as SEPT12 interactors through the yeast 2-hybrid system, including NDC1 transmembrane nucleoporin (NDC1). NDC1 is a major nuclear pore protein, and is critical for nuclear pore complex assembly and nuclear morphology maintenance in mammalian cells. Mutated NDC1 cause gametogenesis defects and skeletal malformations in mice, which were detected spontaneously in the A/J strain. In this study, we characterized the functional effects of SEPT12–NDC1 complexes during mammalian spermiogenesis. In mature human spermatozoa, SEPT12 and NDC1 are majorly colocalized in the centrosome regions; however, NDC1 is only slightly co-expressed with SEPT12 at the annulus of the sperm tail. In addition, SEPT12 interacts with NDC1 in the male germ cell line through coimmunoprecipitation. During murine spermiogenesis, we observed that NDC1 was located at the nuclear membrane of spermatids and at the necks of mature spermatozoa. In male germ cell lines, NDC1 overexpression restricted the localization of SEPT12 to the nucleus and repressed the filament formation of SEPT12. In mice sperm with mutated SEPT12, NDC1 dispersed around the manchette region of the sperm head and annulus, compared with concentrating at the sperm neck of wild-type sperm. These results indicate that SEPT12–NDC1 complexes are involved in mammalian spermiogenesis.

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“…The co-IP analysis was performed according to the procedures in our previous study [37]. The pFLAG- SEPTIN12 plasmids were transfected into cells using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

SEPT12-Microtubule Complexes Are Required for Sperm Head and Tail Formation

Kuo

Chiang

Wang

et al. 2013

IJMS

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The septin gene belongs to a highly conserved family of polymerizing GTP-binding cytoskeletal proteins. SEPTs perform cytoskeletal remodeling, cell polarity, mitosis, and vesicle trafficking by interacting with various cytoskeletons. Our previous studies have indicated that SEPTIN12+/+/+/− chimeras with a SEPTIN12 mutant allele were infertile. Spermatozoa from the vas deferens of chimeric mice indicated an abnormal sperm morphology, decreased sperm count, and immotile sperm. Mutations and genetic variants of SEPTIN12 in infertility cases also caused oligozoospermia and teratozoospermia. We suggest that a loss of SEPT12 affects the biological function of microtublin functions and causes spermiogenesis defects. In the cell model, SEPT12 interacts with α- and β-tubulins by co-immunoprecipitation (co-IP). To determine the precise localization and interactions between SEPT12 and α- and β-tubulins in vivo, we created SEPTIN12-transgene mice. We demonstrate how SEPT12 interacts and co-localizes with α- and β-tubulins during spermiogenesis in these mice. By using shRNA, the loss of SEPT12 transcripts disrupts α- and β-tubulin organization. In addition, losing or decreasing SEPT12 disturbs the morphogenesis of sperm heads and the elongation of sperm tails, the steps of which are coordinated and constructed by α- and β-tubulins, in SEPTIN12+/+/+/− chimeras. In this study, we discovered that the SEPTIN12-microtubule complexes are critical for sperm formation during spermiogenesis.

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Identification and characterization of a novel Rab GTPase-activating protein in spermatids

Cited by 24 publications

References 48 publications

The role of the septin family in spermiogenesis

The role of the septin family in spermiogenesis

SEPT12–NDC1 Complexes Are Required for Mammalian Spermiogenesis

SEPT12-Microtubule Complexes Are Required for Sperm Head and Tail Formation

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