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Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture
- Source :
- Nature Communications, Nature Communications, Nature Publishing Group, 2016, 7, ⟨10.1038/ncomms11097⟩, Nature Communications, 2016, 7, ⟨10.1038/ncomms11097⟩, Nature Communications (7), . (2016), Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016)
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
Abstract
- Mg2+ plays a vital role in platelet function, but despite implications for life-threatening conditions such as stroke or myocardial infarction, the mechanisms controlling [Mg2+]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 (Trpm7fl/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 Trpm7fl/fl-Pf4Cre MKs, which is rescued by Mg2+ 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.<br />Although Mg2+ is vital for platelet activation and aggregation, its regulation in these cells is still largely unknown. Here, the authors show that TRPM7, a cation channel and a protein kinase, regulates thrombopoiesis and platelet size by affecting the cytoskeleton of these cells in mice and humans.
- Subjects :
- 0301 basic medicine
[SDV]Life Sciences [q-bio]
General Physics and Astronomy
DISEASE
Transient receptor potential channel
Mice
Megakaryocyte
ACTOMYOSIN CONTRACTILITY
Homeostasis
Platelet
Magnesium
Thrombopoiesis
Cytoskeleton
Multidisciplinary
Nonmuscle Myosin Type IIA
KINASE TRPM7
3. Good health
Cell biology
Multidisciplinary Sciences
[SDV] Life Sciences [q-bio]
MEGAKARYOCYTE
medicine.anatomical_structure
Science & Technology - Other Topics
Megakaryocytes
Blood Platelets
MIGRATION
Platelet disorder
Science
TRPM Cation Channels
PLATELET DISORDERS
Biology
Protein Serine-Threonine Kinases
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
TRPM7
MD Multidisciplinary
medicine
Animals
Humans
ddc:610
PROPLATELET FORMATION
Science & Technology
MUTATIONS
General Chemistry
Thrombocytopenia
030104 developmental biology
Mutant Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, Nature Publishing Group, 2016, 7, ⟨10.1038/ncomms11097⟩, Nature Communications, 2016, 7, ⟨10.1038/ncomms11097⟩, Nature Communications (7), . (2016), Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016)
- Accession number :
- edsair.doi.dedup.....02fd4ea2cc4192a7f45c3c87aca7c5cf