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Gene Review:

Sept4 - septin 4

Mus musculus

Synonyms: ARTS, Bh5, Brain protein H5, OTTMUSG00000001265, Peanut-like protein 2, ...

Kissel, H. et al., Ihara, M. et al., Zhang, J. et al., Iwaisako, K. et al., Ono, R. et al., et al.

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Disease relevance of Sept4

The sterility is rescued by injection of sperm into oocytes, demonstrating that each Sept4 null spermatozoon carries an intact haploid genome [1].
In vivo, liver fibrosis was consistently more severe in Sept4(-/-) mice than in wild-type littermates in all of the three paradigms of hepatitis/liver fibrosis [2].

High impact information on Sept4

Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4 [3].
RESULTS: Here we show that the mammalian septin H5 is associated with the plasma membrane and specifically binds the phospholipids phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P(2)) and phosphatidylinositol 3,4, 5-trisphosphate (PtdIns(3,4,5)P(3)) [4].
Characterization of the mammalian septin H5: distinct patterns of cytoskeletal and membrane association from other septin proteins [5].
This is consistent with a role of the proapoptotic Sept4 protein ARTS in promoting caspase-mediated removal of cytoplasm via inhibition of XIAP [6].
In Sept4 null spermatozoa, the annulus is replaced by a fragile segment lacking cortical material, beneath which kinesin-mediated intraflagellar transport stalls [1].

Biological context of Sept4

During spermatogenesis, Sept4 proteins were essential for proper mitochondrial architecture and establishment of the annulus, a ring-like structure in the tail region of sperm [6].
The murine septin4 gene (Sept4) has been implicated in diverse cellular functions, including cytokinesis, apoptosis, and tumor suppression [6].
In addition, Sept4 mutant sperm showed defects in the elimination of residual cytoplasm during sperm maturation and had increased staining for the caspase inhibitor XIAP [6].

Anatomical context of Sept4

Sept4-/- male mice are sterile due to defective morphology and motility of the sperm flagellum [1].
A mammalian septin gene Sept4 is expressed mainly in postmitotic neural cells and postmeiotic male germ cells [1].

References

Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa. Ihara, M., Kinoshita, A., Yamada, S., Tanaka, H., Tanigaki, A., Kitano, A., Goto, M., Okubo, K., Nishiyama, H., Ogawa, O., Takahashi, C., Itohara, S., Nishimune, Y., Noda, M., Kinoshita, M. Dev. Cell (2005) [Pubmed]
Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells. Iwaisako, K., Hatano, E., Taura, K., Nakajima, A., Tada, M., Seo, S., Tamaki, N., Sato, F., Ikai, I., Uemoto, S., Kinoshita, M. J. Hepatol. (2008) [Pubmed]
Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4. Ono, R., Ihara, M., Nakajima, H., Ozaki, K., Kataoka-Fujiwara, Y., Taki, T., Nagata, K., Inagaki, M., Yoshida, N., Kitamura, T., Hayashi, Y., Kinoshita, M., Nosaka, T. Mol. Cell. Biol. (2005) [Pubmed]
Phosphatidylinositol polyphosphate binding to the mammalian septin H5 is modulated by GTP. Zhang, J., Kong, C., Xie, H., McPherson, P.S., Grinstein, S., Trimble, W.S. Curr. Biol. (1999) [Pubmed]
Characterization of the mammalian septin H5: distinct patterns of cytoskeletal and membrane association from other septin proteins. Xie, H., Surka, M., Howard, J., Trimble, W.S. Cell Motil. Cytoskeleton (1999) [Pubmed]
The Sept4 septin locus is required for sperm terminal differentiation in mice. Kissel, H., Georgescu, M.M., Larisch, S., Manova, K., Hunnicutt, G.R., Steller, H. Dev. Cell (2005) [Pubmed]

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AGOS_AER238C	Ashbya gossypii ATCC 10895
SEPT4	Bos taurus
C9H17orf47	Canis lupus familiaris
sept4b	Danio rerio
SEPT4	Gallus gallus
SEPT4	Homo sapiens
KLLA0E21583g	Kluyveromyces lactis NRRL Y-1140
SEPT4	Macaca mulatta
MGG_07466	Magnaporthe oryzae 70-15
NCU03795	Neurospora crassa OR74A
SEPT4	Pan troglodytes
CDC12	Saccharomyces cerevisiae S288c
spn4	Schizosaccharomyces pombe 972h-
LOC100485625	Xenopus (Silurana) tropicalis

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