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

J. Biol. Chem., Vol. 279, Issue 25, 26526-26532, June 18, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/25/26526    most recent M401883200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leikina, E. Articles by Chernomordik, L. V. Search for Related Content PubMed PubMed Citation Articles by Leikina, E. Articles by Chernomordik, L. V. Social Bookmarking                      What's this?

Influenza Hemagglutinins Outside of the Contact Zone Are Necessary for Fusion Pore Expansion^*

Eugenia Leikina, Aditya Mittal, Myoung-Soon Cho, Kamran Melikov, Michael M. Kozlov¶, and Leonid V. Chernomordik||

From the Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, NICHD, National Institutes of Health, Bethesda, Maryland 20892-1855 and the Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel

Current models for membrane fusion in diverse biological processes are focused on the local action of fusion proteins present in the contact zone where the proteins anchored in one membrane might interact directly with the other membrane. Are the fusion proteins outside of the contact zone just bystanders? Here we assess the role of these "outsider" proteins in influenza virus hemagglutinin-mediated fusion between red blood cells and either hemagglutinin-expressing cells or viral particles. To selectively inhibit or enhance the actions of hemagglutinin outsiders, the antibodies that bind to hemagglutinin and proteases that cleave it were conjugated to polystyrene microspheres too large to enter the contact zone. We also involved hemagglutinin outsiders into interactions with additional red blood cells. We find the hemagglutinin outsiders to be necessary and sufficient for fusion. Interfering with the activity of the hemagglutinin outsiders inhibited fusion. Selective conversion of hemagglutinin outsiders alone into fusion-competent conformation was sufficient to achieve fusion. The discovered functional role of fusion proteins located outside of the contact zone suggests a tempting analogy to mechanisms by which proteins mediate membrane fission from outside of the fission site.

Received for publication, February 20, 2004 , and in revised form, April 7, 2004.

^* 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.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. 1S–5S.

^¶ Supported by the Human Frontier Science Program Organization.

^|| To whom correspondence should be addressed: NICHD, National Institutes of Health, Bldg. 10, Rm. 10D04, 10 Center Dr., Bethesda, MD 20892-1855. Tel.: 301-594-1128; Fax: 301-480-2916; E-mail: lchern{at}helix.nih.gov.

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

This article has been cited by other articles:

				T. Gattegno, A. Mittal, C. Valansi, K. C.Q. Nguyen, D. H. Hall, L. V. Chernomordik, and B. Podbilewicz Genetic Control of Fusion Pore Expansion in the Epidermis of Caenorhabditis elegans Mol. Biol. Cell, April 1, 2007; 18(4): 1153 - 1166. [Abstract] [Full Text] [PDF]

				O. Lenz, M. T. Dittmar, A. Wagner, B. Ferko, K. Vorauer-Uhl, G. Stiegler, and W. Weissenhorn Trimeric Membrane-anchored gp41 Inhibits HIV Membrane Fusion J. Biol. Chem., February 11, 2005; 280(6): 4095 - 4101. [Abstract] [Full Text] [PDF]