Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture

被引：0

作者：

Simon Stritt

Paquita Nurden

Remi Favier

Marie Favier

Silvia Ferioli

Sanjeev K. Gotru

Judith M M. van Eeuwijk

Harald Schulze

Alan T. Nurden

Michele P. Lambert

Ernest Turro

Stephanie Burger-Stritt

Masayuki Matsushita

Lorenz Mittermeier

Paola Ballerini

Susanna Zierler

Michael A. Laffan

Vladimir Chubanov

Thomas Gudermann

Bernhard Nieswandt

Attila Braun

机构：

[1] Chair of Experimental Biomedicine,Division of Haematology

[2] University Hospital,Department of Paediatrics

[3] University of Würzburg,Department of Haematology

[4] Josef-Schneider-Strasse 2,Department of Internal Medicine I

[5] 97078 Würzburg,Department of Molecular & Cellular Physiology

[6] Germany,undefined

[7] Rudolf Virchow Centre,undefined

[8] University of Würzburg,undefined

[9] Josef-Schneider-Strasse 2,undefined

[10] 97078 Würzburg,undefined

[11] Germany,undefined

[12] Institut Hospitalo-Universitaire LIRYC,undefined

[13] Plateforme Technologique d'Innovation Biomédicale,undefined

[14] Hôpital Xavier Arnozan,undefined

[15] Avenue du Haut Lévêque,undefined

[16] 33604 Pessac,undefined

[17] France,undefined

[18] Assistance Publique—Hôpitaux de Paris,undefined

[19] Haematological Laboratory,undefined

[20] Armand Trousseau Children Hospital,undefined

[21] 26 Avenue du Docteur Arnold-Netter,undefined

[22] 75012 Paris,undefined

[23] France,undefined

[24] Inserm U1170,undefined

[25] Gustave Roussy,undefined

[26] University Paris Sud,undefined

[27] 114 Rue Edouard Vaillant,undefined

[28] 94805 Villejuif,undefined

[29] France,undefined

[30] Inra,undefined

[31] UMR_INRA 1260,undefined

[32] 27 Boulevard Jean Moulin,undefined

[33] 13385 Marseille,undefined

[34] France,undefined

[35] Aix Marseille Université,undefined

[36] 58 Boulevard Charles Livon,undefined

[37] 13284 Marseille,undefined

[38] France,undefined

[39] Inserm UMR_S 1062,undefined

[40] 27 Boulevard Jean Moulin,undefined

[41] 13385 Marseille,undefined

[42] France,undefined

[43] Walther-Straub-Institute for Pharmacology and Toxicology,undefined

[44] Ludwig-Maximilians University Munich,undefined

[45] Goethestraße 33,undefined

[46] 80336 Munich,undefined

[47] Germany,undefined

[48] Children’s Hospital of Philadelphia,undefined

[49] 3401 Civic Center Blvd,undefined

[50] Philadelphia,undefined

来源：

Nature Communications | / 7卷

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摘要：

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.

引用

共 41 条

[1] Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture
Stritt, Simon
Nurden, Paquita
Favier, Remi
Favier, Marie
Ferioli, Silvia
Gotru, Sanjeev K.
van Eeuwijk, Judith M. M.
Schulze, Harald
Nurden, Alan T.
Lambert, Michele P.
Turro, Ernest
Burger-Stritt, Stephanie
Matsushita, Masayuki
Mittermeier, Lorenz
Ballerini, Paola
Zierler, Susanna
Laffan, Michael A.
Chubanov, Vladimir
Gudermann, Thomas
Nieswandt, Bernhard
Braun, Attila
[J]. NATURE COMMUNICATIONS, 2016, 7
[2] Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture
Stritt, S.
Nurden, P.
Favier, R.
Favier, M.
Ferioli, S.
Gotru, K. S.
van Eeuwijk, J. M. M.
Schulze, H.
Nurden, A. T.
Lambert, M. P.
Turro, E.
Burger-Stritt, S.
Matsushita, M.
Mittermeier, L.
Ballerini, P.
Zierler, S.
Laffan, M. A.
Chubanov, V
Gudermann, T.
Nieswandt, B.
Braun, A.
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