title: Navigation through the Plasma Membrane Molecular Landscape Shapes Random Organelle Movement.
abstract: Eukaryotic plasma membrane organization theory has long been controversial, in part due to a dearth of suitably high-resolution techniques to probe molecular architecture in situ and integrate information from diverse data streams [1]. Notably, clustered patterning of membrane proteins is a commonly conserved feature across diverse protein families (reviewed in [2]), including the SNAREs [3], SM proteins [4, 5], ion channels [6, 7], and receptors (e.g., [8]). Much effort has gone into analyzing the behavior of secretory organelles [9-13], and understanding the relationship between the membrane and proximal organelles [4, 5, 12, 14] is an essential goal for cell biology as broad concepts or rules may be established. Here we explore the generally accepted model that vesicles at the plasmalemma are guided by cytoskeletal tracks to specific sites on the membrane that have clustered molecular machinery for secretion [15], organized in part by the local lipid composition [16]. To increase our understanding of these fundamental processes, we integrated nanoscopy and spectroscopy of the secretory machinery with organelle tracking data in a mathematical model, iterating with knockdown cell models. We find that repeated routes followed by successive vesicles, the re-use of similar fusion sites, and the apparently distinct vesicle "pools" are all fashioned by the Brownian behavior of organelles overlaid on navigation between non-reactive secretory protein molecular depots patterned at the plasma membrane.
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Dun
authors.affiliation: Department of Mathematics, Maxwell Institute, MACS, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Lord
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium.
authors.forename: Rhodri S
authors.initials: RS
authors.lastname: Wilson
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium.
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: Kavanagh
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium.
authors.forename: Katarzyna I
authors.initials: KI
authors.lastname: Cialowicz
authors.affiliation: Toronto Western Research Institute, Room 11-432, McLaughlin Wing, 399 Bathurst St., Toronto, ON M5T 2S8, Canada.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Sugita
authors.affiliation: Toronto Western Research Institute, Room 11-432, McLaughlin Wing, 399 Bathurst St., Toronto, ON M5T 2S8, Canada.
authors.forename: Seungmee
authors.initials: S
authors.lastname: Park
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
authors.forename: Annya M
authors.initials: AM
authors.lastname: Smyth
authors.affiliation: The Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papadopulos
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium.
authors.forename: Colin
authors.initials: C
authors.lastname: Rickman
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK; Edinburgh Super-Resolution Imaging Consortium. Electronic address: r.r.duncan@hw.ac.uk.
authors.forename: Rory R
authors.initials: RR
authors.lastname: Duncan
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D015388:Organelles / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D050600:SNARE Proteins
keywords: actin; cytoskeleton; exocytosis; mathematical modeling; microscopy; super-resolution; vesicle