| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RIIA Alter Its Association with Lipid Rafts: Implications for Receptor Signaling1
* Immunology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico; and
Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, CA 94158
Many immunoreceptors have been reported to associate with lipid rafts upon ligand binding. The way in which this association is regulated is still obscure. We investigated the roles for various domains of the human immunoreceptor Fc
RIIA in regulating its association with lipid rafts by determining the resistance of unligated, or ligated and cross-linked, receptors to solubilization by the nonionic detergent Triton X-100, when expressed in RBL-2H3 cells. Deletion of the cytoplasmic domain, or destruction of the cytoplasmic palmitoylation site, had no effect on the association of the receptor with lipid rafts. A transmembrane mutant, A224S, lost the ability to associate with lipid rafts upon receptor cross-linking, whereas transmembrane mutants VA231-2MM and VVAL234-7GISF showed constitutive lipid raft association. Wild-type (WT) FcRIIA and all transmembrane mutants activated Syk, regardless of their association with lipid rafts. WT FcRIIA and mutants that associated with lipid rafts efficiently activated NF-
B, in an ERK-dependent manner. In contrast, WT FcRIIA and the A224S mutant both presented efficient phagocytosis, while VA231-2MM and VVAL234-7GISF mutants presented lower phagocytosis, suggesting that phagocytosis may proceed independently of lipid raft association. These data identify the transmembrane domain of FcRIIA as responsible for regulating its inducible association with lipid rafts and suggest that FcRIIA-mediated responses, like NF-B activation or phagocytosis, can be modulated by lipid raft association of the ligated receptor.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant 36407-M form Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico and by a grant from UC-MEXUS-CONACyT.
2 Address correspondence and reprint requests to Dr. Carlos Rosales, Department of Immunology, Instituto de Investigaciones Biomédicas-Universidad Nacional Autónoma de México, Apartado Postal 70228, Ciudad Universitaria, México D.F.-04510, Mexico. E-mail address: carosal{at}servidor.unam.mx
3 Abbreviations used in this paper: DRM, detergent-resistant membrane domain; TM, transmembrane domain; Cyt, cytoplasmic domain; WT, wild type; HA, hemagglutinin A; PVDF, polyvinylidene fluoride; MFI, mean fluorescence intensity; EC, extracellular domain.
This article has been cited by other articles:
|
|
 |
|
  S. Bournazos, S. P. Hart, L. H. Chamberlain, M. J. Glennie, and I. Dransfield Association of Fc{gamma}RIIa (CD32a) with Lipid Rafts Regulates Ligand Binding Activity J. Immunol., June 15, 2009; 182(12): 8026 - 8036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Clancy and R. Duncan Reovirus FAST Protein Transmembrane Domains Function in a Modular, Primary Sequence-Independent Manner To Mediate Cell-Cell Membrane Fusion J. Virol., April 1, 2009; 83(7): 2941 - 2950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Mao, M. Yamaga, X. Zhu, Y. Wei, H.-Q. Sun, J. Wang, M. Yun, Y. Wang, G. Di Paolo, M. Bennett, et al. Essential and unique roles of PIP5K-{gamma} and -{alpha} in Fc{gamma} receptor-mediated phagocytosis J. Cell Biol., January 26, 2009; 184(2): 281 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Huynh, E. Gershenzon, and S. Grinstein Cholesterol Accumulation by Macrophages Impairs Phagosome Maturation J. Biol. Chem., December 19, 2008; 283(51): 35745 - 35755. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
