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

@article{citeulike:1496131, 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. 10.1242/jcs.03469}, author = {Bouschet, Tristan and Martin, Stephane and Kanamarlapudi, Venkateswarlu and Mundell, Stuart and Henley, Jeremy M.}, citeulike-article-id = {1496131}, citeulike-linkout-0 = {http://dx.doi.org/10.1242/jcs.03469}, citeulike-linkout-1 = {http://jcs.biologists.org/cgi/content/abstract/120/15/2489}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17623778}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17623778}, day = {1}, doi = {10.1242/jcs.03469}, journal = {J Cell Sci}, keywords = {arf6, beta-arrestin, neuroscience}, month = {August}, number = {15}, pages = {2489--2497}, posted-at = {2007-07-26 15:22:36}, priority = {2}, title = {The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network}, url = {http://dx.doi.org/10.1242/jcs.03469}, volume = {120}, year = {2007} }

TY - JOUR ID - citeulike:1496131 L3 - citeulike-article-id:1496131 N2 - 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. 10.1242/jcs.03469 IS - 15 JF - J Cell Sci EP - 2497 TI - The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network VL - 120 SP - 2489 KW - arf6 KW - beta-arrestin KW - neuroscience AU - Bouschet, Tristan AU - Martin, Stephane AU - Kanamarlapudi, Venkateswarlu AU - Mundell, Stuart AU - Henley, Jeremy PY - 2007/08/01/ UR - http://dx.doi.org/10.1242/jcs.03469 ER -