Defining the TLT-1 interactome from resting and activated human platelets.

Autor: Schmoker AM; Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, USA. Electronic address: aschmoke@uvm.edu., Perez Pearson LM; Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, USA; Department of Biology, University of Puerto Rico-Río Piedras, Department of Biology, San Juan, PR, USA., Cruz C; Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, USA; Department of Biology, University of Puerto Rico-Río Piedras, Department of Biology, San Juan, PR, USA., Colon Flores LG; Department of Biology, University of Puerto Rico-Río Piedras, Department of Biology, San Juan, PR, USA., Branfeild S; Department of Biology, University of Puerto Rico-Río Piedras, Department of Biology, San Juan, PR, USA., Pagán Torres FD; Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, USA., Fonseca K; Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, USA., Cantres YM; Translational Proteomics Center, Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA., Salgado Ramirez CA; Translational Proteomics Center, Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA., Melendez LM; Department of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA; Translational Proteomics Center, Comprehensive Cancer Center, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA., Ballif BA; Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, USA. Electronic address: bballif@uvm.edu., Washington AV; Department of Biology, University of Puerto Rico-Río Piedras, Department of Biology, San Juan, PR, USA. Electronic address: anthony.washington@upr.edu.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2020 Mar 20; Vol. 215, pp. 103638. Date of Electronic Publication: 2020 Jan 08.
DOI: 10.1016/j.jprot.2020.103638
Abstrakt: The triggering receptor expressed on myeloid cells (TREM) protein family forms a class of type I transmembrane proteins expressed in immune cells that play important roles in innate and adaptive immune responses. The TREM family member TREM-like transcript 1 (TLT-1, also TREML1) is expressed in megakaryocytes and packaged into platelet granules. TLT-1 binds fibrinogen and plays a role in bleeding initiated by inflammatory insults. Here, we describe a proteomics screen that maps the TLT-1 interactome in resting and activated human platelets. Several identified TLT-1 interactors are involved in cell adhesion and migration, as well as platelet activation. Select interactors, including β 3 -integrin, RACK1, GRB2, and Rabs 5A, 7, and 11A, were additionally characterized in co-immunoprecipitation/immunoblotting experiments. Finally, several phosphorylation sites were found on immunoprecipitated TLT-1, including Thr280, a novel, regulated site on a conserved residue near the TLT-1 ITIM regulatory sequence. SIGNIFICANCE: Platelet function relies on the secretion of active molecules from intracellular vesicles, or granules, which contain soluble and membrane-bound proteins that are essential for platelet aggregation, coagulation reactions, and pathogen defense mechanisms. TLT-1 is sequestered in α-granules and transported to the plasma membrane, where it plays a unique role in hemostasis after inflammatory insults. Despite the known importance of TLT-1 in platelet biology, our knowledge of TLT-1 mechanistic signaling is limited. This study defines the TLT-1 interactome in resting and active human platelets, identifying several novel TLT-1 interactors, as well as TLT-1 phosphorylation sites, all with likely signaling implications in platelet aggregation dynamics.
Competing Interests: Declaration of Competing Interest None declared.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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