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

J. Biol. Chem., Vol. 280, Issue 29, 27004-27012, July 22, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/29/27004    most recent M413735200v1 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 Segura-Morales, C. Articles by Basyuk, E. Search for Related Content PubMed PubMed Citation Articles by Segura-Morales, C. Articles by Basyuk, E. Social Bookmarking                      What's this?

Tsg101 and Alix Interact with Murine Leukemia Virus Gag and Cooperate with Nedd4 Ubiquitin Ligases during Budding^*

Carolina Segura-Morales, Christina Pescia, Christine Chatellard-Causse, Remy Sadoul, Edouard Bertrand, and Eugenia Basyuk||

From the IGMM-CNRS, 1919 Route de Mende 34293, Montpellier Cedex 5 and Neurodégénérescence et Plasticité, EMI 0108, INSERM/UJF, 38043 Grenoble 9, France

Retroviruses use endosomal machinery to bud out of infected cells, and various Gag proteins recruit this machinery by interacting with either of three cellular factors as follows: ubiquitin ligases of the Nedd4 family, Tsg101, or Alix/Aip1. Here we show that the murine leukemia virus Gag has the unique ability to interact with all three factors. Small interfering RNAs against Tsg101 or Alix and dominant-negative forms of Nedd4 can all reduce production of virus-like particles. However, inactivating the Nedd4-binding site abolishes budding, whereas disrupting Tsg101 or Alix binding has milder effects. Nedd4 ubiquitin ligases are therefore essential, and Tsg101 and Alix play auxiliary roles. Most interestingly, overexpression of Alix can stimulate the release of Gag, and this occurs independently of most Alix partners Tsg101, Cin85, Alg-2, and endophilins. In addition, Gag mutants that do not bind Tsg101 or Alix concentrate on late endosomes and become very sensitive to dominant-negative forms of Nedd4 that do not conjugate ubiquitin. This suggests that the direct interaction of Gag with Tsg101 and Alix favors budding from the plasma membrane and relieves a requirement for ubiquitination by Nedd4.1. Other Nedd4-dependent Gag proteins also contain binding sites for Tsg101 or Alix, suggesting that this could be a common feature of retroviruses.

Received for publication, December 6, 2004 , and in revised form, May 18, 2005.

^* 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.

^|| To whom correspondence should be addressed. Tel.: 33-467613647; Fax: 33-467040231; E-mail: Eugenia.Basyuk{at}igmm.cnrs.fr.

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

This article has been cited by other articles:

				Y. Sabo, N. Laham-Karam, and E. Bacharach Basal Budding and Replication of the Murine Leukemia Virus Are Independent of the Gag L Domains J. Virol., October 1, 2008; 82(19): 9770 - 9775. [Abstract] [Full Text] [PDF]

				H.-Y. Chung, E. Morita, U. von Schwedler, B. Muller, H.-G. Krausslich, and W. I. Sundquist NEDD4L Overexpression Rescues the Release and Infectivity of Human Immunodeficiency Virus Type 1 Constructs Lacking PTAP and YPXL Late Domains J. Virol., May 15, 2008; 82(10): 4884 - 4897. [Abstract] [Full Text] [PDF]

				M. Gladnikoff and I. Rousso Directly Monitoring Individual Retrovirus Budding Events Using Atomic Force Microscopy Biophys. J., January 1, 2008; 94(1): 320 - 326. [Abstract] [Full Text] [PDF]

				C. Lambert, T. Doring, and R. Prange Hepatitis B Virus Maturation Is Sensitive to Functional Inhibition of ESCRT-III, Vps4, and {gamma}2-Adaptin J. Virol., September 1, 2007; 81(17): 9050 - 9060. [Abstract] [Full Text] [PDF]

				E. Nikko and B. Andre Split-Ubiquitin Two-Hybrid Assay To Analyze Protein-Protein Interactions at the Endosome: Application to Saccharomyces cerevisiae Bro1 Interacting with ESCRT Complexes, the Doa4 Ubiquitin Hydrolase, and the Rsp5 Ubiquitin Ligase Eukaryot. Cell, August 1, 2007; 6(8): 1266 - 1277. [Abstract] [Full Text] [PDF]

				G. Camus, C. Segura-Morales, D. Molle, S. Lopez-Verges, C. Begon-Pescia, C. Cazevieille, P. Schu, E. Bertrand, C. Berlioz-Torrent, and E. Basyuk The Clathrin Adaptor Complex AP-1 Binds HIV-1 and MLV Gag and Facilitates Their Budding Mol. Biol. Cell, August 1, 2007; 18(8): 3193 - 3203. [Abstract] [Full Text] [PDF]

				K. M. Honeychurch, G. Yang, R. Jordan, and D. E. Hruby The Vaccinia Virus F13L YPPL Motif Is Required for Efficient Release of Extracellular Enveloped Virus J. Virol., July 1, 2007; 81(13): 7310 - 7315. [Abstract] [Full Text] [PDF]

				F. Bouamr, B. R. Houck-Loomis, M. De Los Santos, R. J. Casaday, M. C. Johnson, and S. P. Goff The C-Terminal Portion of the Hrs Protein Interacts with Tsg101 and Interferes with Human Immunodeficiency Virus Type 1 Gag Particle Production J. Virol., March 15, 2007; 81(6): 2909 - 2922. [Abstract] [Full Text] [PDF]

				M. W. McNatt, I. McKittrick, M. West, and G. Odorizzi Direct Binding to Rsp5 Mediates Ubiquitin-independent Sorting of Sna3 via the Multivesicular Body Pathway Mol. Biol. Cell, February 1, 2007; 18(2): 697 - 706. [Abstract] [Full Text] [PDF]

				C. Langelier, U. K. von Schwedler, R. D. Fisher, I. De Domenico, P. L. White, C. P. Hill, J. Kaplan, D. Ward, and W. I. Sundquist Human ESCRT-II Complex and Its Role in Human Immunodeficiency Virus Type 1 Release J. Virol., October 1, 2006; 80(19): 9465 - 9480. [Abstract] [Full Text] [PDF]

				M. Rost, S. Mann, C. Lambert, T. Doring, N. Thome, and R. Prange {gamma}2-Adaptin, a Novel Ubiquitin-interacting Adaptor, and Nedd4 Ubiquitin Ligase Control Hepatitis B Virus Maturation J. Biol. Chem., September 29, 2006; 281(39): 29297 - 29308. [Abstract] [Full Text] [PDF]

				G. Odorizzi The multiple personalities of Alix. J. Cell Sci., August 1, 2006; 119(Pt 15): 3025 - 3032. [Abstract] [Full Text] [PDF]

				O. Staub and D. Rotin Role of Ubiquitylation in Cellular Membrane Transport Physiol Rev, April 1, 2006; 86(2): 669 - 707. [Abstract] [Full Text] [PDF]

				C. Chen, O. Vincent, J. Jin, O. A. Weisz, and R. C. Montelaro Functions of Early (AP-2) and Late (AIP1/ALIX) Endocytic Proteins in Equine Infectious Anemia Virus Budding J. Biol. Chem., December 9, 2005; 280(49): 40474 - 40480. [Abstract] [Full Text] [PDF]