spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 27 February 2007
doi: 10.1242/jcs.03415

Journal of Cell Science 120, 1126-1133 (2007)
Published by The Company of Biologists 2007
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.03415v1
120/6/1126    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rey, M.
Right arrow Articles by Sánchez-Madrid, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rey, M.
Right arrow Articles by Sánchez-Madrid, F.

Research Article

Myosin IIA is involved in the endocytosis of CXCR4 induced by SDF-1{alpha}

Mercedes Rey1, Agustín Valenzuela-Fernández1, Ana Urzainqui1, María Yáñez-Mó1, Manuel Pérez-Martínez1, Petronila Penela2, Federico Mayor, Jr2 and Francisco Sánchez-Madrid1,*

1 Servicio de Inmunología, Hospital Universitario de la Princesa, Diego de León, 62, 28006 Madrid, Spain
2 Departamento de Biología Molecular y Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain

* Author for correspondence (e-mail: fsanchez.hlpr{at}salud.madrid.org)

Accepted 22 January 2007

Endocytosis of chemokine receptors regulates signal transduction initiated by chemokines, but the molecular mechanisms underlying this process are not fully defined. In this work, we assessed the involvement of the motor protein nonmuscle myosin heavy chain IIA (MIIA) in the endocytosis of CXCR4 induced by SDF-1{alpha} (also known as CXCL12) in T lymphocytes. Overexpression of the C-terminal half of MIIA inhibited the ligand-induced endocytosis of CXCR4, but not that of transferrin receptor. Targeting MIIA either by silencing its expression with small interfering RNA (siRNA) or by blebbistatin treatment also inhibited endocytosis of CXCR4. Inhibition of endocytosis of CXCR4 by targeting endogenous MIIA resulted in an increased migration of T cells induced by SDF-1{alpha}, and in the inhibition of the HIV-1-Env antifusogenic activity of this chemokine. Coimmunoprecipitation and protein-protein binding studies demonstrated that MIIA interacts with both the cytoplasmic tail of CXCR4 and beta-arrestin. Moreover, SDF-1{alpha} promotes a rapid MIIA-beta-arrestin dissociation. Our data reveal a novel role for MIIA in CXCR4 endocytosis, which involves its dynamic association with beta-arrestin and highlights the role of endogenous MIIA as a regulator of CXCR4 internalization and, therefore, the onset of SDF-1{alpha} signaling.

Key words: Chemokines, T cells, Signal transduction




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Xiao, D. B. McClatchy, A. K. Shukla, Y. Zhao, M. Chen, S. K. Shenoy, J. R. Yates III, and R. J. Lefkowitz
Functional specialization of beta-arrestin interactions revealed by proteomic analysis
PNAS, July 17, 2007; 104(29): 12011 - 12016.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007