![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 5, 2375-2387, May 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
q/11 Association
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
Submitted December 12, 2003;
Revised February 17, 2004;
Accepted February 23, 2004
Monitoring Editor: Guido Guidotti
By means of a variety of intracellular scaffolding proteins, a vast number of heterotrimeric G protein–coupled receptors (GPCRs) may achieve specificity in signaling through a much smaller number of heterotrimeric G proteins. Members of the tetraspanin family organize extensive complexes of cell surface proteins and thus have the potential to act as GPCR scaffolds; however, tetraspanin-GPCR complexes had not previously been described. We now show that a GPCR, GPR56/TM7XN1, and heterotrimeric G protein subunits, G
q, G11, and G
, associate specifically with tetraspanins and CD81, but not with other tetraspanins. CD9 Complexes of GPR56 with CD9 and CD81 remained intact when fully solubilized and were resistant to cholesterol depletion. Hence they do not depend on detergent-insoluble, raft-like membrane microdomains for stability. A central role for CD81 in promoting or stabilizing a GPR56-CD81-Gq/11 complex was revealed by CD81 immunodepletion and reexpression experiments. Finally, antibody engagement of cell surface CD81 or cell activation with phorbol ester revealed two distinct mechanisms by which GPR56-CD81-Gq/11 complexes can be dynamically regulated. These data reveal a potential role for tetraspanins CD9 and CD81 as GPCR scaffolding proteins.
Current address: Department of Biological Sciences, University of Iowa, Iowa City, IA 52242.
* Corresponding author. E-mail address: martin_hemler{at}dfci.harvard.edu.
This article has been cited by other articles:
|
|
 |
|
  S. Li, Z. Jin, S. Koirala, L. Bu, L. Xu, R. O. Hynes, C. A. Walsh, G. Corfas, and X. Piao GPR56 Regulates Pial Basement Membrane Integrity and Cortical Lamination J. Neurosci., May 28, 2008; 28(22): 5817 - 5826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iguchi, K. Sakata, K. Yoshizaki, K. Tago, N. Mizuno, and H. Itoh Orphan G Protein-coupled Receptor GPR56 Regulates Neural Progenitor Cell Migration via a G{alpha}12/13 and Rho Pathway J. Biol. Chem., May 23, 2008; 283(21): 14469 - 14478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Harris, M. J. Farquhar, C. J. Mee, C. Davis, G. M. Reynolds, A. Jennings, K. Hu, F. Yuan, H. Deng, S. G. Hubscher, et al. CD81 and Claudin 1 Coreceptor Association: Role in Hepatitis C Virus Entry J. Virol., May 15, 2008; 82(10): 5007 - 5020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Griffiths, K. J. Heesom, and D. J. Anstee Normal prion protein trafficking in cultured human erythroblasts Blood, December 15, 2007; 110(13): 4518 - 4525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. V. Kovalenko, X. H. Yang, and M. E. Hemler A Novel Cysteine Cross-linking Method Reveals a Direct Association between Claudin-1 and Tetraspanin CD9 Mol. Cell. Proteomics, November 1, 2007; 6(11): 1855 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Jin, I. Tietjen, L. Bu, L. Liu-Yesucevitz, S. K. Gaur, C. A. Walsh, and X. Piao Disease-associated mutations affect GPR56 protein trafficking and cell surface expression Hum. Mol. Genet., August 15, 2007; 16(16): 1972 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zsombok and K. M. Jacobs Postsynaptic Currents Prior to Onset of Epileptiform Activity in Rat Microgyria J Neurophysiol, July 1, 2007; 98(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ke, R. Sundaram, G. Liu, J. Chionis, W. Fan, C. Rogers, T. Awad, M. Grifman, D. Yu, F. Wong-Staal, et al. Orphan G protein-coupled receptor GPR56 plays a role in cell transformation and tumorigenesis involving the cell adhesion pathway Mol. Cancer Ther., June 1, 2007; 6(6): 1840 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Akazawa, T. Date, K. Morikawa, A. Murayama, M. Miyamoto, M. Kaga, H. Barth, T. F. Baumert, J. Dubuisson, and T. Wakita CD81 Expression Is Important for the Permissiveness of Huh7 Cell Clones for Heterogeneous Hepatitis C Virus Infection J. Virol., May 15, 2007; 81(10): 5036 - 5045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Iismaa, G. E. Begg, and R. M. Graham Cross-Linking Transglutaminases with G Protein-Coupled Receptor Signaling Sci. Signal., September 19, 2006; 2006(353): pe34 - pe34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gesierich, I. Berezovskiy, E. Ryschich, and M. Zoller Systemic Induction of the Angiogenesis Switch by the Tetraspanin D6.1A/CO-029. Cancer Res., July 15, 2006; 66(14): 7083 - 7094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xu, S. Begum, J. D. Hearn, and R. O. Hynes GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis PNAS, June 13, 2006; 103(24): 9023 - 9028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Le Naour, M. Andre, C. Greco, M. Billard, B. Sordat, J.-F. Emile, F. Lanza, C. Boucheix, and E. Rubinstein Profiling of the Tetraspanin Web of Human Colon Cancer Cells Mol. Cell. Proteomics, May 1, 2006; 5(5): 845 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Shoham, R. Rajapaksa, C.-C. Kuo, J. Haimovich, and S. Levy Building of the Tetraspanin Web: Distinct Structural Domains of CD81 Function in Different Cellular Compartments Mol. Cell. Biol., February 15, 2006; 26(4): 1373 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mizuno, H. Kokubu, M. Sato, A. Nishimura, J. Yamauchi, H. Kurose, and H. Itoh G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration PNAS, August 30, 2005; 102(35): 12365 - 12370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Levy and T. Shoham Protein-Protein Interactions in the Tetraspanin Web Physiology, August 1, 2005; 20(4): 218 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lentschat, H. Karahashi, K. S. Michelsen, L. S. Thomas, W. Zhang, S. N. Vogel, and M. Arditi Mastoparan, a G Protein Agonist Peptide, Differentially Modulates TLR4- and TLR2-Mediated Signaling in Human Endothelial Cells and Murine Macrophages J. Immunol., April 1, 2005; 174(7): 4252 - 4261. [Abstract] [Full Text] [PDF]
|
|
