Rnd3-induced cell rounding requires interaction with Plexin-B2

TY - JOUR

T1 - Rnd3-induced cell rounding requires interaction with Plexin-B2

AU - McColl, Brad

AU - Garg, Ritu

AU - Riou, Philippe

AU - Riento, Kirsi

AU - Ridley, Anne J.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Rnd proteins are atypical members of the Rho GTPase family that induce actin cytoskeletal reorganization and cell rounding. Rnd proteins have been reported to bind to the intracellular domain of several plexin receptors, but whether plexins contribute to the Rndinduced rounding response is not known. Here we show that Rnd3 interacts preferentially with plexin-B2 of the three plexin-B proteins, whereas Rnd2 interacts with all three B-type plexins, and Rnd1 shows only very weak interaction with plexin-B proteins in immunoprecipitations. Plexin-B1 has been reported to act as a GAP for R-Ras and/or Rap1 proteins. We show that all three plexin-B proteins interact with R-Ras and Rap1, but Rnd proteins do not alter this interaction or R-Ras or Rap1 activity.We demonstrate that plexin- B2 promotes Rnd3-induced cell rounding and loss of stress fibres, and enhances the inhibition of HeLa cell invasion by Rnd3. We identify the amino acids in Rnd3 that are required for plexin-B2 interaction, and show that mutation of these amino acids prevents Rnd3-induced morphological changes. These results indicate that plexin-B2 is a downstream target for Rnd3, which contributes to its cellular function.

AB - Rnd proteins are atypical members of the Rho GTPase family that induce actin cytoskeletal reorganization and cell rounding. Rnd proteins have been reported to bind to the intracellular domain of several plexin receptors, but whether plexins contribute to the Rndinduced rounding response is not known. Here we show that Rnd3 interacts preferentially with plexin-B2 of the three plexin-B proteins, whereas Rnd2 interacts with all three B-type plexins, and Rnd1 shows only very weak interaction with plexin-B proteins in immunoprecipitations. Plexin-B1 has been reported to act as a GAP for R-Ras and/or Rap1 proteins. We show that all three plexin-B proteins interact with R-Ras and Rap1, but Rnd proteins do not alter this interaction or R-Ras or Rap1 activity.We demonstrate that plexin- B2 promotes Rnd3-induced cell rounding and loss of stress fibres, and enhances the inhibition of HeLa cell invasion by Rnd3. We identify the amino acids in Rnd3 that are required for plexin-B2 interaction, and show that mutation of these amino acids prevents Rnd3-induced morphological changes. These results indicate that plexin-B2 is a downstream target for Rnd3, which contributes to its cellular function.

KW - Actin cytoskeleton

KW - Cell shape

KW - Plexin

KW - Rho GTPase

UR - http://www.scopus.com/inward/record.url?scp=84995485596&partnerID=8YFLogxK

U2 - 10.1242/jcs.192211

DO - 10.1242/jcs.192211

M3 - Article

AN - SCOPUS:84995485596

SN - 0021-9533

VL - 129

SP - 4046

EP - 4056

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 21

ER -