A Rac–PAK1–Ajuba feedback loop stabilizes cadherin complexes via coordination of spatiotemporal signaling with actin remodeling at cell–cell contacts

Arias-Romero

Ayyanathan

Bailly

Belen Martin-Martin

Betson

Bokoch

Braga

Daub

Deacon

Delva

DerMardirossian

Drees

Ehrlich

Fehon

Flaiz

Goodwin

Goyal

Gregory Longmore

Hansen

Haraguchi

Hirota

Hodivala

Ivanov

Kadrmas

Kanungo

Kasia Smolarczyk

Kisseleva

Kumar

Lambert

Langer

Lleres

Lozano

Makrogianneli

Marie

Maryke Carstens

Maryse Bailly

Miller

Montoya-Durango

Mège

Nagai

Nakagawa

Nakamura

Nelson

Oppermann

Ozdamar

Pratt

Reiko Daigaku

Reinhard

Rennefahrt

Rheinwald

Riento

Rimm

Rolli-Derkinderen

Sander

Self

Smutny

Sébastien Nola

Takaishi

Takeichi

Tanos

Thoreson

Tolias

Vania M.M. Braga

Vasioukhin

Vigil

Vincent

Wirtz-Peitz

Yamada

Zegers

Zhang

Zhao

The Journal of Cell Biology

English

PubMed

Nola, S

Daigaku, R

Smolarczyk, K

Carstens, M

Martin-Martin, B

Longmore, G

Bailly, M

Braga, VMM

Spiral - Imperial College Digital Repository

Ajuba is required for Rac activation and maintenance of E-cadherin adhesion

Maintenance of stable E-cadherin–dependent adhesion is essential for epithelial function. The small GTPase Rac is activated by initial cadherin clustering, but the precise mechanisms underlying Rac-dependent junction stabilization are not well understood. Ajuba, a LIM domain protein, colocalizes with cadherins, yet Ajuba function at junctions is unknown. We show that, in Ajuba-depleted cells, Rac activation and actin accumulation at cadherin receptors was impaired, and junctions did not sustain mechanical stress. The Rac effector PAK1 was also transiently activated upon cell–cell adhesion and directly phosphorylated Ajuba (Thr172). Interestingly, similar to Ajuba depletion, blocking PAK1 activation perturbed junction maintenance and actin recruitment. Expression of phosphomimetic Ajuba rescued the effects of PAK1 inhibition. Ajuba bound directly to Rac·GDP or Rac·GTP, but phosphorylated Ajuba interacted preferentially with active Rac. Rather than facilitating Rac recruitment to junctions, Ajuba modulated Rac dynamics at contacts depending on its phosphorylation status. Thus, a Rac–PAK1–Ajuba feedback loop integrates spatiotemporal signaling with actin remodeling at cell–cell contacts and stabilizes preassembled cadherin complexes.</jats:p

Crossref

Nola, Sébastien

Daigaku, Reiko

Smolarczyk, Kasia

Carstens, Maryke

Martin-Martin, Belen

Longmore, Gregory

Bailly, Maryse

Braga, Vania M.M.

Digital Commons@Becker

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http://jcb.rupress.org/content/jcb/195/5/855.full.pdf

Ajuba is required for Rac activation and maintenance of E-cadherin adhesion

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