Extracellular matrix component Receptor
Cells use a wide spectrum of proteins and mechanisms to recognize their environment. Evidence demonstrates that extracellular matrix components receptors can be used by Mks to control the site of platelet formation and release. Whether and how extracellular matrix component receptor activity is regulated during thrombopoiesis in vivo is not known. To progress towards a better understanding of these critical mechanisms, significantly improved knowledge of the physical, cellular and biochemical interactions in the bone marrow environment is needed. Integrins are the major human receptors for cell adhesion on extracellular matrix components, however a variety of other interaction mechanisms are possible. Besides integrin alpha2beta1 and GPVI, expression and function of other collagen receptors on human megakaryocytes are unknown. Discoidin domain receptors (DDR1 and DDR2) are tyrosine-kinase collagen receptors that are stimulated by fibrillar and basement membrane collagens and mediate cell adhesion and migration in different tissues. We recently discovered that DDR1 is expressed by both human megakaryocytes and platelets. DDR1 is activated upon megakaryocyte adhesion on fibrillar type I collagen and regulates megakaryocyte Syk-mediated migration through activation of the tyrosine phosphatase SHP1. Altogether, these data point out that DDR1 may represent an important new regulator of megakaryocyte function.