The calcium-sensing receptor changes cell shape via a β-arrestin-1-ARNO-ARF6-ELMO protein network

T Bouschet, SAR Martin, V Kanamarlapudi, SJ Mundell, JM Henley

Research output: Contribution to journalArticle (Academic Journal)peer-review

37 Citations (Scopus)

Abstract

G-protein-coupled receptors (GPCRs) transduce the binding of extracellular stimuli into intracellular signalling cascades that can lead to morphological changes. Here, we demonstrate that stimulation of the calcium-sensing receptor (CaSR), a GPCR that promotes chemotaxis by detecting increases in extracellular calcium, triggers plasma membrane (PM) ruffling via a pathway that involves beta-arrestin 1, Arf nucleotide binding site opener (ARNO), ADP-ribosylating factor 6 (ARF6) and engulfment and cell motility protein (ELMO). Expression of dominant negative beta-arrestin 1 or its knockdown with siRNA impaired the CaSR-induced PM ruffling response. Expression of a catalytically inactive ARNO also reduced CaSR-induced PM ruffling. Furthermore, beta-arrestin 1 co-immunoprecipitated with the CaSR and ARNO under resting conditions. Agonist treatment did not markedly alter beta-arrestin 1 binding to the CaSR or to ARNO but it did elicit the translocation and colocalisation of the CaSR, beta-arrestin 1 and ARNO to membrane protrusions. Furthermore, ARF6 and ELMO, two proteins known to couple ARNO to the cytoskeleton, were required for CaSR-dependent morphological changes and translocated to the PM ruffles. These data suggest that cells ruffle upon CaSR stimulation via a mechanism that involves translocation of beta-arrestin 1 pre-assembled with the CaSR or ARNO, and that ELMO plays an essential role in this CaSR-signalling-induced cytoskeletal reorganisation.
Translated title of the contributionThe calcium-sensing receptor changes cell shape via a β-arrestin-1-ARNO-ARF6-ELMO protein network
Original languageEnglish
Pages (from-to)2489 - 2497
Number of pages8
JournalJournal of Cell Science
Volume120 (15)
DOIs
Publication statusPublished - Aug 2007

Bibliographical note

Publisher: Company of Biologists

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