| First Author | Stritt S | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11097 | PubMed ID | 27020697 |
| Mgi Jnum | J:236828 | Mgi Id | MGI:5807328 |
| Doi | 10.1038/ncomms11097 | Citation | Stritt S, et al. (2016) Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg(2+) homeostasis and cytoskeletal architecture. Nat Commun 7:11097 |
| abstractText | Mg(2+) plays a vital role in platelet function, but despite implications for life-threatening conditions such as stroke or myocardial infarction, the mechanisms controlling [Mg(2+)]i in megakaryocytes (MKs) and platelets are largely unknown. Transient receptor potential melastatin-like 7 channel (TRPM7) is a ubiquitous, constitutively active cation channel with a cytosolic alpha-kinase domain that is critical for embryonic development and cell survival. Here we report that impaired channel function of TRPM7 in MKs causes macrothrombocytopenia in mice (Trpm7(fl/fl-Pf4Cre)) and likely in several members of a human pedigree that, in addition, suffer from atrial fibrillation. The defect in platelet biogenesis is mainly caused by cytoskeletal alterations resulting in impaired proplatelet formation by Trpm7(fl/fl-Pf4Cre) MKs, which is rescued by Mg(2+) supplementation or chemical inhibition of non-muscle myosin IIA heavy chain activity. Collectively, our findings reveal that TRPM7 dysfunction may cause macrothrombocytopenia in humans and mice. |
