Non-muscle myosin IIA and IIB differentially affect the traffic and signalling of the thrombopoietin receptor

The Thrombopoietin Receptor (TpoR) is essential to the production of platelets. Activation of the surface receptor by its ligand thrombopoietin (TPO) leads to the lineage-specific differentiation of the haematopoietic stem and myeloid progenitors into megakaryocytes and platelets. Moreover, platelet surface TpoR scavenges the serum TPO, creating a feedback mechanism that regulates the availability of TPO, ensuring platelet homeostasis. Therefore, the surface expression of the receptor must be tightly regulated during the process of megakaryopoiesis. Megakaryopoiesis is accompanied by alterations in the expression of the two non-muscle Myosin isoforms IIA and IIB. Using cell line models of megakaryopoiesis and COS7 cells that preferentially express the NMIIB isoform, the traffic, surface expression, and signalling of TpoR was found to be augmented by the expression of NMIIA. This was attributed to NMIIA-dependent remodelling of the cortical actin network. Consequently, ROCK inhibition generated an altered cortical actin network along with reduced surface expression and signalling of TpoR. Thus, our study demonstrated that megakaryopoiesis-dependent alteration in NMIIA expression contributed to enhanced TpoR surface expression and signalling.

Actin; JAK-STAT signalling; Non-muscle myosin II; Thrombopoietin receptor.