In and out: Traffic and dynamics of thrombopoietin receptor

• Published in: Journal of cellular and molecular medicine 2021-10, Vol.25 (19), p.9073-9083
• Main Authors: Roy, Anita, Shrivastva, Saurabh, Naseer, Saadia
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Binding sites; Bone marrow; Calreticulin - genetics; Calreticulin - metabolism; Cytokines; Dimerization; Disease Susceptibility; Drug Discovery; Gene Expression Regulation - drug effects; Golgi Apparatus - metabolism; Granulocytes; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; JAK2; Janus Kinase 2 - metabolism; Kinases; Leukemia; Ligands; Localization; Mutagenesis; Mutation; myeloproliferation; Osteoprogenitor cells; Protein Binding; Protein Multimerization; Protein Transport; Proteins; receptor dimerization; Receptors, Thrombopoietin - chemistry; Receptors, Thrombopoietin - genetics; Receptors, Thrombopoietin - metabolism; Review; Reviews; Signal Transduction; Stem cells; Structure-Activity Relationship; Thrombocytopenia; Thrombocytopenic purpura; Thrombocytosis; Thrombopoiesis; Thrombopoietin; Thrombopoietin - metabolism; thrombopoietin receptor; traffic; Tumors; TYK2 Kinase - metabolism
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16878

Thrombopoiesis had long been a challenging area of study due to the rarity of megakaryocyte precursors in the bone marrow and the incomplete understanding of its regulatory cytokines. A breakthrough was achieved in the early 1990s with the discovery of the thrombopoietin receptor (TpoR) and its ligand thrombopoietin (TPO). This accelerated research in thrombopoiesis, including the uncovering of the molecular basis of myeloproliferative neoplasms (MPN) and the advent of drugs to treat thrombocytopenic purpura. TpoR mutations affecting its membrane dynamics or transport were increasingly associated with pathologies such as MPN and thrombocytosis. It also became apparent that TpoR affected hematopoietic stem cell (HSC) quiescence while priming hematopoietic stem cells (HSCs) towards the megakaryocyte lineage. Thorough knowledge of TpoR surface localization, dimerization, dynamics and stability is therefore crucial to understanding thrombopoiesis and related pathologies. In this review, we will discuss the mechanisms of TpoR traffic. We will focus on the recent progress in TpoR membrane dynamics and highlight the areas that remain unexplored.