title: Homozygous loss of mouse tetraspanin CD82 enhances integrin αIIbβ3 expression and clot retraction in platelets.
abstract: Integrin αIIbβ3 is critical for platelet-mediated blood clotting. Tetraspanins are well-established regulators of integrins and genetic loss of tetraspanin CD151 or TSSC6 in mice leads to increased bleeding due to inadequate integrin αIIbβ3 outside-in signaling. Conversely, mild but enhanced integrin αIIbβ3 activation and hyperaggregation is observed in CD9 and CD63 null mice respectively. CD82 is reportedly expressed in platelets; however its function is unknown. Using genetically engineered CD82 null mice, we investigated the role of the tetraspanin CD82 in platelet activation. Loss of CD82 resulted in reduced bleed times in vivo. CD82 was present on the surface of both human and mouse platelets, and its levels did not change upon platelet activation or degranulation. No differences in platelet activation, degranulation, or aggregation in response to ADP or collagen were detected in CD82 null mice. However, the kinetics of clot retraction was enhanced, which was intrinsic to the CD82-null platelets. Integrin αIIbβ3 surface expression was elevated on the platelets from CD82 null mice and they displayed enhanced adhesion and tyrosine kinase signaling on fibrinogen. This is the first report on CD82 function in platelets; which we found intrinsically modulates clot retraction, integrin αIIbβ3 expression, cell adhesion, and tyrosine signaling.
authors.affiliation: Lab of Integrin Signaling, Van Andel Research Institute, Grand Rapids, MI 49503 United States.
authors.forename: Kristen
authors.initials: K
authors.lastname: Uchtmann
authors.affiliation: Lab of Integrin Signaling, Van Andel Research Institute, Grand Rapids, MI 49503 United States.
authors.forename: Electa R
authors.initials: ER
authors.lastname: Park
authors.affiliation: Lab of Integrin Signaling, Van Andel Research Institute, Grand Rapids, MI 49503 United States.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bergsma
authors.affiliation: Lab of Integrin Signaling, Van Andel Research Institute, Grand Rapids, MI 49503 United States.
authors.forename: Justin
authors.initials: J
authors.lastname: Segula
authors.affiliation: Lab of Integrin Signaling, Van Andel Research Institute, Grand Rapids, MI 49503 United States.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Edick
authors.affiliation: Lab of Integrin Signaling, Van Andel Research Institute, Grand Rapids, MI 49503 United States. Electronic address: cindy.miranti@vai.org.
authors.forename: Cindy K
authors.initials: CK
authors.lastname: Miranti
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003018:Clot Retraction / Q000235:genetics*; D006801:Humans; D051861:Kangai-1 Protein / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism
chemical_list: D051861:Kangai-1 Protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: Blood platelets; Cell adhesion; Disease model-animals; Integrins; Tetraspanins