Title: Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4
Authors: Nilius, Bernd ×
Prenen, Jean
Tang, Jisen
Wang, Chunbo
Owsianik, Grzegorz
Janssens, Annelies
Voets, Thomas
Zhu, Michael X #
Issue Date: Feb-2005
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:280 issue:8 pages:6423-6433
Abstract: TRPM4, a Ca(2+)-activated cation channel of the transient receptor potential superfamily, undergoes a fast desensitization to Ca(2+). The mechanisms underlying the alterations in Ca(2+) sensitivity are unknown. Here we show that cytoplasmic ATP reversed Ca(2+) sensitivity after desensitization, whereas mutations to putative ATP binding sites resulted in faster and more complete desensitization. Phorbol ester-induced activation of protein kinase C (PKC) increased the Ca(2+) sensitivity of wild-type TRPM4 but not of two mutants mutated at putative PKC phosphorylation sites. Overexpression of a calmodulin mutant unable to bind Ca(2+) dramatically reduced TRPM4 activation. We identified five Ca(2+)-calmodulin binding sites in TRPM4 and showed that deletion of any of the three C-terminal sites strongly impaired current activation by reducing Ca(2+) sensitivity and shifting the voltage dependence of activation to very positive potentials. Thus, the Ca(2+) sensitivity of TRPM4 is regulated by ATP, PKC-dependent phosphorylation, and calmodulin binding at the C terminus.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Department of Cellular and Molecular Medicine - miscellaneous
Laboratory of Ion Channel Research
× corresponding author
# (joint) last author

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