title: Gap junctions and connexin hemichannels underpin hemostasis and thrombosis.
abstract: BACKGROUND
  Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have examined the role of connexins in platelets, blood cells that circulate in isolation but on tissue injury adhere to each other and the vessel wall to prevent blood loss and to facilitate wound repair.
  
  
  RESULTS
  We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses before platelet-platelet contact and reduced laser-induced thrombosis in vivo in mice. Deletion of the Cx37 gene (Gja4) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion, and clot retraction, indicating an important role for connexin37 hemichannels and gap junctions in platelet thrombus function.
  
  
  CONCLUSIONS
  Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of hemostasis and thrombosis and represent potential therapeutic targets.
authors.affiliation: Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Hopkins Bldg, Reading, RG6 6UB, UK.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Vaiyapuri
authors.forename: Chris I
authors.initials: CI
authors.lastname: Jones
authors.forename: Parvathy
authors.initials: P
authors.lastname: Sasikumar
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Moraes
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Munger
authors.forename: Joy R
authors.initials: JR
authors.lastname: Wright
authors.forename: Marfoua S
authors.initials: MS
authors.lastname: Ali
authors.forename: Tanya
authors.initials: T
authors.lastname: Sage
authors.forename: William J
authors.initials: WJ
authors.lastname: Kaiser
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Stain
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Bye
authors.forename: Sarah
authors.initials: S
authors.lastname: Jones
authors.forename: Ernesto
authors.initials: E
authors.lastname: Oviedo-Orta
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Simon
authors.forename: Martyn P
authors.initials: MP
authors.lastname: Mahaut-Smith
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gibbins
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology; D003018:Clot Retraction / Q000502:physiology; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006367:HeLa Cells; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013927:Thrombosis / Q000503:physiopathology*; D000097002:Gap Junction beta-1 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D002229:Carbenoxolone; D018031:Connexin 43; D017630:Connexins; D010975:Platelet Aggregation Inhibitors; D000097002:Gap Junction beta-1 Protein; D000097006:Gap Junction alpha-4 Protein; C484032:GJD4 protein, human