TAILIEUCHUNG - Báo cáo khoa học: Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1

The small G protein Rap1 regulates diverse cellular processes such as inte-grin activation, cell adhesion, cell–cell junction formation and cell polarity. It is crucial to identify Rap1 effectors to better understand the signalling pathways controlling these processes. | ễFEBS Journal Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1 Sophie Beraud-Dufour1 Romain Gautier1 Corinne Albiges-Rizo2 Pierre Chardin1 and Eva Faurobert1 1 UMR 6097 CNRS-UNSA Institut de Pharmacologie Moleculaire et Cellulaire Vabonne France 2 CRI U823 Universite Joseph Fourier Institut Albert Bonniot equipe 1 DYSAD Grenoble France Keywords CCM1 FERM domain Kritl microtubules PIP2 Correspondence E. Faurobert CRI U823 Universite Joseph Fourier Institut Albert Bonniot equipe 1 DYSAD Site Sante La Tronche BP170 38042 Grenoble Cedex 9 France Fax 33 476 54 94 25 Tel 33 476 54 94 74 E-mail faurobert@ Received 15 May 2007 revised 13 July 2007 accepted 24 August 2007 doi The small G protein Rap1 regulates diverse cellular processes such as inte-grin activation cell adhesion cell-cell junction formation and cell polarity. It is crucial to identify Rap1 effectors to better understand the signalling pathways controlling these processes. Krev interaction trapped 1 Kritl a protein with FERM band four-point-one ezrin radixin moesin domain was identified as a Rap1 partner in a yeast two-hybrid screen but this interaction was not confirmed in subsequent studies. As the evidence suggests a role for Krit1 in Rap1-dependent pathways we readdressed this question. In the present study we demonstrate by biochemical assays that Kritl interacts with RaplA preferentially its GTP-bound form. We show that like other FERM proteins Kritl adopts two conformations a closed conformation in which its N-terminal NPAY motif interacts with its C-ter-minus and an opened conformation bound to integrin cytoplasmic domain associated protein ICAP -1 a negative regulator of focal adhesion assembly. We show that a ternary complex can form in vitro between Kritl Rap1 and ICAP-1 and that Rap1 binds the Krit1 FERM domain in both closed and opened conformations. Unlike ICAP-1 Rapl does

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