title: Actin mediates the nanoscale membrane organization of the clustered membrane protein influenza hemagglutinin.
abstract: The influenza viral membrane protein hemagglutinin (HA) is required at high concentrations on virion and host-cell membranes for infectivity. Because the role of actin in membrane organization is not completely understood, we quantified the relationship between HA and host-cell actin at the nanoscale. Results obtained using superresolution fluorescence photoactivation localization microscopy (FPALM) in nonpolarized cells show that HA clusters colocalize with actin-rich membrane regions (ARMRs). Individual molecular trajectories in live cells indicate restricted HA mobility in ARMRs, and actin disruption caused specific changes to HA clustering. Surprisingly, the actin-binding protein cofilin was excluded from some regions within several hundred nanometers of HA clusters, suggesting that HA clusters or adjacent proteins within the same clusters influence local actin structure. Thus, with the use of imaging, we demonstrate a dynamic relationship between glycoprotein membrane organization and the actin cytoskeleton at the nanoscale.
authors.affiliation: Department of Physics and Astronomy, University of Maine, Orono, ME, USA.
authors.forename: Manasa V
authors.initials: MV
authors.lastname: Gudheti
authors.forename: Nikki M
authors.initials: NM
authors.lastname: Curthoys
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Gould
authors.forename: Dahan
authors.initials: D
authors.lastname: Kim
authors.forename: Mudalige S
authors.initials: MS
authors.lastname: Gunewardene
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Gabor
authors.forename: Julie A
authors.initials: JA
authors.lastname: Gosse
authors.forename: Carol H
authors.initials: CH
authors.lastname: Kim
authors.forename: Joshua
authors.initials: J
authors.lastname: Zimmerberg
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Hess
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D053121:Influenza A Virus, H2N2 Subtype / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D055503:Protein Multimerization
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019267:Hemagglutinin Glycoproteins, Influenza Virus