Septins Regulate Actin Organization and Cell-cycle Arrest Through Nuclear Accumulation of NCK Mediated by SOCS7

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2007 Sep 7

PMID 17803907

Citations 106

Authors

Brandon E Kremer

Laura A Adang

Ian G Macara

Affiliations

Soon will be listed here.

Abstract

Mammalian septins are GTP-binding proteins the functions of which are not well understood. Knockdown of SEPT2, 6, and 7 causes stress fibers to disintegrate and cells to lose polarity. We now show that this phenotype is induced by nuclear accumulation of the adaptor protein NCK, as the effects can be reversed or induced by cytoplasmic or nuclear NCK, respectively. NCK is carried into the nucleus by SOCS7 (suppressor of cytokine signaling 7), which possesses nuclear import/export signals. SOCS7 interacts with septins and NCK through distinct domains. DNA damage induces actin and septin rearrangement and rapid nuclear accumulation of NCK and SOCS7. Moreover, NCK expression is essential for cell-cycle arrest. The septin-SOCS7-NCK axis intersects with the canonical DNA damage cascade downstream of ATM/ATR and is essential for p53 Ser15 phosphorylation. These data illuminate an unanticipated connection between septins, SOCS7, NCK signaling, and the DNA damage response.

Citing Articles

ECM-dependent regulation of septin 7 in focal adhesions promotes mechanosensing and functional response in fibroblasts.

Sturgess W, Packirisamy S, Geneidy R, Nordenfelt P, Swaminathan V iScience. 2024; 27(12):111355.

PMID: 39650732 PMC: 11625310. DOI: 10.1016/j.isci.2024.111355.

Dysregulation of septin cytoskeletal organization in the trabecular meshwork contributes to ocular hypertension.

Maddala R, Gorijavolu P, Lankford L, Skiba N, Challa P, Singh R JCI Insight. 2024; 9(23).

PMID: 39641270 PMC: 11623952. DOI: 10.1172/jci.insight.179468.

Septins as key players in spermatogenesis, fertilisation and pre-implantation embryogenic cytoplasmic dynamics.

Al-Ali H, Baig A, Alkhanjari R, Murtaza Z, Alhajeri M, Elbahrawi R Cell Commun Signal. 2024; 22(1):523.

PMID: 39468561 PMC: 11514797. DOI: 10.1186/s12964-024-01889-z.

The Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7.

Herrera-Uribe J, Convery O, ALmohammadi D, Weinberg F, Stevenson N Inflammation. 2024; .

PMID: 39460806 DOI: 10.1007/s10753-024-02163-7.

Genome-wide association study reveals the underlying regulatory mechanisms of red blood traits in Anadara granosa.

He X, Liao Y, Yu G, Wang S, Bao Y BMC Genomics. 2024; 25(1):931.

PMID: 39367301 PMC: 11452991. DOI: 10.1186/s12864-024-10857-3.

References

Oegema K, Savoian M, Mitchison T, Field C . Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol. 2000; 150(3):539-52. PMC: 2175195. DOI: 10.1083/jcb.150.3.539. View

Matuoka K, Miki H, Takahashi K, Takenawa T . A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs. Biochem Biophys Res Commun. 1997; 239(2):488-92. DOI: 10.1006/bbrc.1997.7492. View

Joberty G, Perlungher R, Sheffield P, Kinoshita M, Noda M, Haystead T . Borg proteins control septin organization and are negatively regulated by Cdc42. Nat Cell Biol. 2001; 3(10):861-6. DOI: 10.1038/ncb1001-861. View

Buday L, Wunderlich L, Tamas P . The Nck family of adapter proteins: regulators of actin cytoskeleton. Cell Signal. 2002; 14(9):723-31. DOI: 10.1016/s0898-6568(02)00027-x. View

Martin K, Slack J, Boerner S, Martin C, Parsons J . Integrin connections map: to infinity and beyond. Science. 2002; 296(5573):1652-3. DOI: 10.1126/science.296.5573.1652. View

Kusch J, Meyer A, Snyder M, Barral Y . Microtubule capture by the cleavage apparatus is required for proper spindle positioning in yeast. Genes Dev. 2002; 16(13):1627-39. PMC: 186372. DOI: 10.1101/gad.222602. View

Surka M, Tsang C, Trimble W . The mammalian septin MSF localizes with microtubules and is required for completion of cytokinesis. Mol Biol Cell. 2002; 13(10):3532-45. PMC: 129964. DOI: 10.1091/mbc.e02-01-0042. View

Kinoshita M, Field C, Coughlin M, Straight A, Mitchison T . Self- and actin-templated assembly of Mammalian septins. Dev Cell. 2002; 3(6):791-802. DOI: 10.1016/s1534-5807(02)00366-0. View

Vega I, Hsu S . The septin protein Nedd5 associates with both the exocyst complex and microtubules and disruption of its GTPase activity promotes aberrant neurite sprouting in PC12 cells. Neuroreport. 2003; 14(1):31-7. DOI: 10.1097/00001756-200301200-00006. View

10.

Sheffield P, Oliver C, Kremer B, Sheng S, Shao Z, Macara I . Borg/septin interactions and the assembly of mammalian septin heterodimers, trimers, and filaments. J Biol Chem. 2002; 278(5):3483-8. DOI: 10.1074/jbc.M209701200. View

11.

Castillon G, Adames N, Rosello C, Seidel H, Longtine M, Cooper J . Septins have a dual role in controlling mitotic exit in budding yeast. Curr Biol. 2003; 13(8):654-8. DOI: 10.1016/s0960-9822(03)00247-1. View

12.

Bladt F, Aippersbach E, Gelkop S, Strasser G, Nash P, Tafuri A . The murine Nck SH2/SH3 adaptors are important for the development of mesoderm-derived embryonic structures and for regulating the cellular actin network. Mol Cell Biol. 2003; 23(13):4586-97. PMC: 164855. DOI: 10.1128/MCB.23.13.4586-4597.2003. View

13.

Lew D . The morphogenesis checkpoint: how yeast cells watch their figures. Curr Opin Cell Biol. 2003; 15(6):648-53. DOI: 10.1016/j.ceb.2003.09.001. View

14.

Martens N, Wery M, Wang P, Braet F, Gertler A, Hooghe R . The suppressor of cytokine signaling (SOCS)-7 interacts with the actin cytoskeleton through vinexin. Exp Cell Res. 2004; 298(1):239-48. DOI: 10.1016/j.yexcr.2004.04.002. View

15.

Xue J, Tsang C, Gai W, Malladi C, Trimble W, Rostas J . Septin 3 (G-septin) is a developmentally regulated phosphoprotein enriched in presynaptic nerve terminals. J Neurochem. 2004; 91(3):579-90. DOI: 10.1111/j.1471-4159.2004.02755.x. View

16.

Fox M . A model for the computer analysis of synchronous DNA distributions obtained by flow cytometry. Cytometry. 1980; 1(1):71-7. DOI: 10.1002/cyto.990010114. View

17.

Richards S, Lounsbury K, Carey K, Macara I . A nuclear export signal is essential for the cytosolic localization of the Ran binding protein, RanBP1. J Cell Biol. 1996; 134(5):1157-68. PMC: 2120988. DOI: 10.1083/jcb.134.5.1157. View

18.

Longtine M, DeMarini D, Valencik M, Fares H, de Virgilio C, Pringle J . The septins: roles in cytokinesis and other processes. Curr Opin Cell Biol. 1996; 8(1):106-19. DOI: 10.1016/s0955-0674(96)80054-8. View

19.

Kinoshita M, Kumar S, Mizoguchi A, Ide C, Kinoshita A, Haraguchi T . Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures. Genes Dev. 1997; 11(12):1535-47. DOI: 10.1101/gad.11.12.1535. View

20.

Smolka M, Chen S, Maddox P, Enserink J, Albuquerque C, Wei X . An FHA domain-mediated protein interaction network of Rad53 reveals its role in polarized cell growth. J Cell Biol. 2006; 175(5):743-53. PMC: 2064674. DOI: 10.1083/jcb.200605081. View