HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 16, 16125-16134, April 22, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/16/16125    most recent M500940200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, J. Articles by Saltiel, A. R. Search for Related Content PubMed PubMed Citation Articles by Liu, J. Articles by Saltiel, A. R. Social Bookmarking                      What's this?

The Stomatin/Prohibitin/Flotillin/HflK/C Domain of Flotillin-1 Contains Distinct Sequences That Direct Plasma Membrane Localization and Protein Interactions in 3T3-L1 Adipocytes^*

Jun Liu, Stephanie M. DeYoung, Mei Zhang, Lisa H. Dold, and Alan R. Saltiel

From the Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109

Flotillin-1 is a lipid raft-associated protein that has been implicated in various cellular processes. We examined the subcellular distribution of flotillin-1 in different cell types and found that localization is cell type-specific. Flotillin-1 relocates from a cytoplasmic compartment to the plasma membrane upon the differentiation of 3T3-L1 adipocytes. To delineate the structural determinants necessary for its localization, we generated a series of truncation mutants of flotillin-1. Wild type flotillin-1 has two putative hydrophobic domains and is localized to lipid raft microdomains at the plasma membrane. Flotillin-1 fragments lacking the N-terminal hydrophobic stretch are excluded from the lipid raft compartments but remain at the plasma membrane. On the other hand, mutants with the second hydrophobic region deleted fail to traffic to the plasma membrane but are instead found in intracellular granule-like structures. Flotillin-1 specifically interacts with the adaptor protein CAP, the Src family kinase Fyn, and cortical F-actin in lipid raft microdomains in adipocytes. Furthermore, CAP and Fyn associate with different regions in the N-terminal sequences of flotillin-1. These results furthered our understanding for how flotillin-1 can function as a molecular link between lipid rafts of the plasma membrane and a multimeric signaling complex at the actin cytoskeleton.

Received for publication, January 25, 2005 , and in revised form, February 14, 2005.

^* This work was supported in part by National Institutes of Health Grants DK61618 and DK60591. 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.

Supported by NIDDK Postdoctoral NRSA Fellowship F32 DK064551 from the National Institutes of Health.

To whom correspondence should be addressed: Life Sciences Institute, University of Michigan, 210 Washtenaw Ave., 3rd Floor 2216, Ann Arbor, MI 48109. Tel.: 734-615-9787; Fax: 734-936-2888; E-mail: saltiel{at}umich.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. G. Kirchhof, L. A. Chau, C. D. Lemke, S. Vardhana, P. J. Darlington, M. E. Marquez, R. Taylor, K. Rizkalla, I. Blanca, M. L. Dustin, et al. Modulation of T Cell Activation by Stomatin-Like Protein 2 J. Immunol., August 1, 2008; 181(3): 1927 - 1936. [Abstract] [Full Text] [PDF]

				M. Zhang, J. Liu, A. Cheng, S. M. DeYoung, and A. R. Saltiel Identification of CAP as a Costameric Protein that Interacts with Filamin C Mol. Biol. Cell, December 1, 2007; 18(12): 4731 - 4740. [Abstract] [Full Text] [PDF]

				M. M. P. Pearce, Y. Wang, G. G. Kelley, and R. J. H. Wojcikiewicz SPFH2 Mediates the Endoplasmic Reticulum-associated Degradation of Inositol 1,4,5-Trisphosphate Receptors and Other Substrates in Mammalian Cells J. Biol. Chem., July 13, 2007; 282(28): 20104 - 20115. [Abstract] [Full Text] [PDF]

				C. Neumann-Giesen, I. Fernow, M. Amaddii, and R. Tikkanen Role of EGF-induced tyrosine phosphorylation of reggie-1/flotillin-2 in cell spreading and signaling to the actin cytoskeleton J. Cell Sci., February 1, 2007; 120(3): 395 - 406. [Abstract] [Full Text] [PDF]

				X. Liu and C. Jefcoate 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Epidermal Growth Factor Cooperatively Suppress Peroxisome Proliferator-Activated Receptor-{gamma}1 Stimulation and Restore Focal Adhesion Complexes during Adipogenesis: Selective Contributions of Src, Rho, and Erk Distinguish These Overlapping Processes in C3H10T1/2 Cells Mol. Pharmacol., December 1, 2006; 70(6): 1902 - 1915. [Abstract] [Full Text] [PDF]

				E. Umlauf, M. Mairhofer, and R. Prohaska Characterization of the Stomatin Domain Involved in Homo-oligomerization and Lipid Raft Association J. Biol. Chem., August 18, 2006; 281(33): 23349 - 23356. [Abstract] [Full Text] [PDF]

				D. T. Browman, M. E. Resek, L. D. Zajchowski, and S. M. Robbins Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER J. Cell Sci., August 1, 2006; 119(15): 3149 - 3160. [Abstract] [Full Text] [PDF]

				M. Inoue, S.-H. Chiang, L. Chang, X.-W. Chen, and A. R. Saltiel Compartmentalization of the Exocyst Complex in Lipid Rafts Controls Glut4 Vesicle Tethering Mol. Biol. Cell, May 1, 2006; 17(5): 2303 - 2311. [Abstract] [Full Text] [PDF]

				L. Pelletier, P. Guillaumot, B. Freche, C. Luquain, D. Christiansen, S. Brugiere, J. Garin, and S. N. Manie {gamma}-Secretase-Dependent Proteolysis of CD44 Promotes Neoplastic Transformation of Rat Fibroblastic Cells. Cancer Res., April 1, 2006; 66(7): 3681 - 3687. [Abstract] [Full Text] [PDF]