title: Nanoclustering as a dominant feature of plasma membrane organization.
abstract: Early studies have revealed that some mammalian plasma membrane proteins exist in small nanoclusters. The advent of super-resolution microscopy has corroborated and extended this picture, and led to the suggestion that many, if not most, membrane proteins are clustered at the plasma membrane at nanoscale lengths. In this Commentary, we present selected examples of glycosylphosphatidyl-anchored proteins, Ras family members and several immune receptors that provide evidence for nanoclustering. We advocate the view that nanoclustering is an important part of the hierarchical organization of proteins in the plasma membrane. According to this emerging picture, nanoclusters can be organized on the mesoscale to form microdomains that are capable of supporting cell adhesion, pathogen binding and immune cell-cell recognition amongst other functions. Yet, a number of outstanding issues concerning nanoclusters remain open, including the details of their molecular composition, biogenesis, size, stability, function and regulation. Notions about these details are put forth and suggestions are made about nanocluster function and why this general feature of protein nanoclustering appears to be so prevalent.
authors.affiliation: ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels (Barcelona), Spain ICREA-Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain maria.garcia-parajo@icfo.es frap@med.unc.edu.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Garcia-Parajo
authors.affiliation: Nanobiophysics, MIRA Institute for Biomedical Technology and Technical Medicine and MESA+ Institute for Nanotechnology, University of Twente, 7522 NB Enschede, The Netherlands Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cambi
authors.affiliation: ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels (Barcelona), Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Torreno-Pina
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Thompson
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA maria.garcia-parajo@icfo.es frap@med.unc.edu.
authors.forename: Ken
authors.initials: K
authors.lastname: Jacobson
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism* / Q000648:ultrastructure; D008853:Microscopy / Q000379:methods; D053758:Nanoparticles; D066329:Protein Aggregates; D011971:Receptors, Immunologic / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D066329:Protein Aggregates; D011971:Receptors, Immunologic; D018631:ras Proteins
keywords: Plasma membrane; Protein nanoclustering; Super-resolution microscopy