TY  - JOUR
A1  - Stritt, Simon
A1  - Nurden, Paquita
A1  - Favier, Remi
A1  - Favier, Marie
A1  - Ferioli, Silvia
A1  - Gotru, Sanjeev K.
A1  - van Eeuwijk, Judith M.M.
A1  - Schulze, Harald
A1  - Nurden, Alan T.
A1  - Lambert, Michele P.
A1  - Turro, Ernest
A1  - Burger-Stritt, Stephanie
A1  - Matsushita, Masayuki
A1  - Mittermeier, Lorenz
A1  - Ballerini, Paola
A1  - Zierler, Susanna
A1  - Laffan, Michael A.
A1  - Chubanov, Vladimir
A1  - Gudermann, Thomas
A1  - Nieswandt, Bernhard
A1  - Braun, Attila
T1  - Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg\(^{2+}\) homeostasis and cytoskeletal architecture
JF  - Nature Communications
N2  - 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 α-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.
KW  - Cytoskeleton
KW  - homeostasisIon channels
KW  - thrombopoiesis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173843
VL  - 7
ER  -