TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

Kristopher Clark, Jeroen Middelbeek, Edwin Lasonder, Natalia Dulianinova, Nick A. Morrice, Alexey G. Ryazanov, Anne R. Bresnick, Carl G. Figdor, Frank N. van Leeuwen

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca2+- and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOH-termini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.

Original languageEnglish (US)
Pages (from-to)788-801
Number of pages14
JournalJournal of Molecular Biology
Volume378
Issue number4
DOIs
StatePublished - May 9 2008

Fingerprint

Nonmuscle Myosin Type IIA
Protein Stability
Myosin Type II
Phosphorylation
Myosin Heavy Chains
Phosphotransferases
Actomyosin
Cytoskeleton
Aspartic Acid
Alanine
Tail
Amino Acids
Mutation
Neoplasms

Keywords

  • actin
  • cytoskeleton
  • myosin IIA
  • phosphorylation
  • TRPM7

ASJC Scopus subject areas

  • Virology

Cite this

Clark, K., Middelbeek, J., Lasonder, E., Dulianinova, N., Morrice, N. A., Ryazanov, A. G., ... van Leeuwen, F. N. (2008). TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation. Journal of Molecular Biology, 378(4), 788-801. https://doi.org/10.1016/j.jmb.2008.02.057

TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation. / Clark, Kristopher; Middelbeek, Jeroen; Lasonder, Edwin; Dulianinova, Natalia; Morrice, Nick A.; Ryazanov, Alexey G.; Bresnick, Anne R.; Figdor, Carl G.; van Leeuwen, Frank N.

In: Journal of Molecular Biology, Vol. 378, No. 4, 09.05.2008, p. 788-801.

Research output: Contribution to journalArticle

Clark, K, Middelbeek, J, Lasonder, E, Dulianinova, N, Morrice, NA, Ryazanov, AG, Bresnick, AR, Figdor, CG & van Leeuwen, FN 2008, 'TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation', Journal of Molecular Biology, vol. 378, no. 4, pp. 788-801. https://doi.org/10.1016/j.jmb.2008.02.057
Clark, Kristopher ; Middelbeek, Jeroen ; Lasonder, Edwin ; Dulianinova, Natalia ; Morrice, Nick A. ; Ryazanov, Alexey G. ; Bresnick, Anne R. ; Figdor, Carl G. ; van Leeuwen, Frank N. / TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation. In: Journal of Molecular Biology. 2008 ; Vol. 378, No. 4. pp. 788-801.
@article{650d77aab5554f28b5ec1ef9e9f88069,
title = "TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation",
abstract = "Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca2+- and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOH-termini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.",
keywords = "actin, cytoskeleton, myosin IIA, phosphorylation, TRPM7",
author = "Kristopher Clark and Jeroen Middelbeek and Edwin Lasonder and Natalia Dulianinova and Morrice, {Nick A.} and Ryazanov, {Alexey G.} and Bresnick, {Anne R.} and Figdor, {Carl G.} and {van Leeuwen}, {Frank N.}",
year = "2008",
month = "5",
day = "9",
doi = "10.1016/j.jmb.2008.02.057",
language = "English (US)",
volume = "378",
pages = "788--801",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - TRPM7 Regulates Myosin IIA Filament Stability and Protein Localization by Heavy Chain Phosphorylation

AU - Clark, Kristopher

AU - Middelbeek, Jeroen

AU - Lasonder, Edwin

AU - Dulianinova, Natalia

AU - Morrice, Nick A.

AU - Ryazanov, Alexey G.

AU - Bresnick, Anne R.

AU - Figdor, Carl G.

AU - van Leeuwen, Frank N.

PY - 2008/5/9

Y1 - 2008/5/9

N2 - Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca2+- and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOH-termini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.

AB - Deregulation of myosin II-based contractility contributes to the pathogenesis of human diseases, such as cancer, which underscores the necessity for tight spatial and temporal control of myosin II activity. Recently, we demonstrated that activation of the mammalian α-kinase TRPM7 inhibits myosin II-based contractility in a Ca2+- and kinase-dependent manner. However, the molecular mechanism is poorly defined. Here, we demonstrate that TRPM7 phosphorylates the COOH-termini of both mouse and human myosin IIA heavy chains-the COOH-terminus being a region that is critical for filament stability. Phosphorylated residues were mapped to Thr1800, Ser1803 and Ser1808. Mutation of these residues to alanine and that to aspartic acid lead to an increase and a decrease, respectively, in myosin IIA incorporation into the actomyosin cytoskeleton and accordingly affect subcellular localization. In conclusion, our data demonstrate that TRPM7 regulates myosin IIA filament stability and localization by phosphorylating a short stretch of amino acids within the α-helical tail of the myosin IIA heavy chain.

KW - actin

KW - cytoskeleton

KW - myosin IIA

KW - phosphorylation

KW - TRPM7

UR - http://www.scopus.com/inward/record.url?scp=41949091771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41949091771&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2008.02.057

DO - 10.1016/j.jmb.2008.02.057

M3 - Article

VL - 378

SP - 788

EP - 801

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -