The Role of Platelet Syntaxins in Endocytosis

Abstract

In healthy patients, platelets serve as the first line of defense in forming a hemostatic plug when damage to the vasculature is detected. Hemostasis is a balancing act, however, where hyperactive platelets can cause unwanted blood clots which may lead to heart attack or stroke, while hypoactive platelets can cause excessive bleeding. For this reason, examining the proteins critical to platelet function and understanding the bleeding phenotype when these proteins are knocked out can provide potential drug targets and help explain and diagnose platelet disorders. In addition to their role in hemostasis, platelets act as vascular “sentries,” patrolling the vasculature for damage and endocytosing small molecules and viral particles they encounter [1]. While the exact purpose of platelet endocytosis of viral particles is unknown, studies have shown that AIDS patients have increased chances of experiencing a thrombotic event [2], which implies that the uptake of the HIV virus by platelets could be implicated in this disparity, perhaps by altering platelet function. Platelets contain SNARE (soluble N‐ethylmaleimide sensitive fusion protein attachment protein receptor) proteins which are known to control trafficking in most cells [3] but this trafficking role has not been established in platelets, making them an attractive target of study. To this end, we created Syntaxin 2, Syntaxin 4 (two t‐SNARE proteins) and double knock out mice to study the endocytic capabilities of their platelets. Platelets from the Syntaxin 4 and double knock out mice showed a defect in the uptake of total fibrinogen while Syntaxin 4 knockouts did not show a defect in uptake of transferrin.Support or Funding InformationThis work is supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (HL56652 and HL138179), and a Veterans Affairs Merit Award to SWW.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.