Bves Directly Interacts with GEFT, and Controls Cell Shape and Movement Through Regulation of Rac1/Cdc42 Activity

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jun 11

PMID 18541910

Citations 40

Authors

T K Smith

H A Hager

R Francis

D M Kilkenny

C W Lo

D M Bader

Affiliations

Soon will be listed here.

Abstract

Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. This interaction represents the first identification of any protein that has a direct physical interaction with any member of the Popdc family. Bves and GEFT are shown to colocalize in adult skeletal muscle. We also demonstrate that exogenous expression of Bves reduces Rac1 and Cdc42 activity levels while not affecting levels of active RhoA. Consistent with a repression of Rac1 and Cdc42 activity, we show changes in speed of cell locomotion and cell roundness also result from exogenous expression of Bves. Modulation of Rho-family GTPase signaling by Bves would be highly consistent with previously described phenotypes occurring upon disruption of Bves function in a wide variety of model systems. Therefore, we propose Bves as a novel regulator of the Rac1 and Cdc42 signaling cascades.

Citing Articles

Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.

Rinne S, Kiper A, Jacob R, Ortiz-Bonnin B, Schindler R, Fischer S iScience. 2024; 27(5):109696.

PMID: 38689644 PMC: 11059135. DOI: 10.1016/j.isci.2024.109696.

Systemic AAV9.BVES delivery ameliorates muscular dystrophy in a mouse model of LGMDR25.

Li H, Wang P, Hsu E, Pinckard K, Stanford K, Han R Mol Ther. 2022; 31(2):398-408.

PMID: 36433649 PMC: 9931600. DOI: 10.1016/j.ymthe.2022.11.012.

Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis.

Han P, Lei Y, Liu J, Liu J, Huang H, Tian D Cell Commun Signal. 2022; 20(1):149.

PMID: 36123685 PMC: 9487093. DOI: 10.1186/s12964-022-00962-9.

cAMP Signaling in Cancer: A PKA-CREB and EPAC-Centric Approach.

Ahmed M, Alghamdi A, Islam S, Lee J, Lee Y Cells. 2022; 11(13).

PMID: 35805104 PMC: 9266045. DOI: 10.3390/cells11132020.

GEFT aberrant expression in soft tissue sarcomas.

Liu Y, Qi S, Meng L, Zhang L, Pang Y, Cui W Transl Cancer Res. 2022; 8(1):141-149.

PMID: 35116743 PMC: 8798328. DOI: 10.21037/tcr.2019.01.16.

References

Chiang S, BAUMANN C, Kanzaki M, Thurmond D, Watson R, Neudauer C . Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature. 2001; 410(6831):944-8. DOI: 10.1038/35073608. View

Stramer B, Wood W, Galko M, Redd M, Jacinto A, Parkhurst S . Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration. J Cell Biol. 2005; 168(4):567-73. PMC: 2171743. DOI: 10.1083/jcb.200405120. View

Kwan K, Kirschner M . A microtubule-binding Rho-GEF controls cell morphology during convergent extension of Xenopus laevis. Development. 2005; 132(20):4599-610. PMC: 1783841. DOI: 10.1242/dev.02041. View

Osler M, Bader D . Bves expression during avian embryogenesis. Dev Dyn. 2004; 229(3):658-67. DOI: 10.1002/dvdy.10490. View

Bishop A, Hall A . Rho GTPases and their effector proteins. Biochem J. 2000; 348 Pt 2:241-55. PMC: 1221060. View

Etienne-Manneville S, Hall A . Rho GTPases in cell biology. Nature. 2002; 420(6916):629-35. DOI: 10.1038/nature01148. View

Woolner S, Jacinto A, Martin P . The small GTPase Rac plays multiple roles in epithelial sheet fusion--dynamic studies of Drosophila dorsal closure. Dev Biol. 2005; 282(1):163-73. DOI: 10.1016/j.ydbio.2005.03.005. View

Soukoulis V, Reddy S, Pooley R, Feng Y, Walsh C, Bader D . Cytoplasmic LEK1 is a regulator of microtubule function through its interaction with the LIS1 pathway. Proc Natl Acad Sci U S A. 2005; 102(24):8549-54. PMC: 1150833. DOI: 10.1073/pnas.0502303102. View

Souchet M, Portales-Casamar E, Mazurais D, Schmidt S, Leger I, Robert P . Human p63RhoGEF, a novel RhoA-specific guanine nucleotide exchange factor, is localized in cardiac sarcomere. J Cell Sci. 2002; 115(Pt 3):629-40. DOI: 10.1242/jcs.115.3.629. View

10.

Ripley A, Chang M, Bader D . Bves is expressed in the epithelial components of the retina, lens, and cornea. Invest Ophthalmol Vis Sci. 2004; 45(8):2475-83. DOI: 10.1167/iovs.04-0013. View

11.

Nobes C . Rho GTPases and cell migration-fibroblast wound healing. Methods Enzymol. 2000; 325:441-9. DOI: 10.1016/s0076-6879(00)25464-5. View

12.

Vasavada T, DiAngelo J, Duncan M . Developmental expression of Pop1/Bves. J Histochem Cytochem. 2004; 52(3):371-7. DOI: 10.1177/002215540405200308. View

13.

Fenteany G, Janmey P, Stossel T . Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets. Curr Biol. 2000; 10(14):831-8. DOI: 10.1016/s0960-9822(00)00579-0. View

14.

Liang Y, Yu W, Li Y, Yang Z, Yan X, Huang Q . Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein. J Cell Biol. 2004; 164(4):557-66. PMC: 2171987. DOI: 10.1083/jcb.200308058. View

15.

Bryan B, Mitchell D, Zhao L, Ma W, Stafford L, Teng B . Modulation of muscle regeneration, myogenesis, and adipogenesis by the Rho family guanine nucleotide exchange factor GEFT. Mol Cell Biol. 2005; 25(24):11089-101. PMC: 1316953. DOI: 10.1128/MCB.25.24.11089-11101.2005. View

16.

Russo C, Gao Y, Mancini P, Vanni C, Porotto M, Falasca M . Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain. J Biol Chem. 2001; 276(22):19524-31. DOI: 10.1074/jbc.M009742200. View

17.

Andree B, Hillemann T, Kessler-Icekson G, Schmitt-John T, Jockusch H, Arnold H . Isolation and characterization of the novel popeye gene family expressed in skeletal muscle and heart. Dev Biol. 2000; 223(2):371-82. DOI: 10.1006/dbio.2000.9751. View

18.

Ripley A, Osler M, Wright C, Bader D . Xbves is a regulator of epithelial movement during early Xenopus laevis development. Proc Natl Acad Sci U S A. 2006; 103(3):614-9. PMC: 1334639. DOI: 10.1073/pnas.0506095103. View

19.

Brand T . The Popeye domain-containing gene family. Cell Biochem Biophys. 2005; 43(1):95-103. DOI: 10.1385/CBB:43:1:095. View

20.

Wada A, Reese D, Bader D . Bves: prototype of a new class of cell adhesion molecules expressed during coronary artery development. Development. 2001; 128(11):2085-93. DOI: 10.1242/dev.128.11.2085. View