RRC ID 57662
Author Yamaguchi S, Tanimoto A, Iwasa S, Otsuguro K.
Title TRPM4 and TRPM5 Channels Share Crucial Amino Acid Residues for Ca2+ Sensitivity but Not Significance of PI(4,5)P2.
Journal Int J Mol Sci
Abstract Transient receptor potential melastatin member 4 (TRPM4) and 5 (TRPM5) channels are Ca2+-activated nonselective cation channels. Intracellular Ca2+ is the most important regulator for them to open, though PI(4,5)P2, a membrane phosphoinositide, has been reported to regulate their Ca2+-sensitivities. We previously reported that negatively-charged amino acid residues near and in the TRP domain are necessary for the normal Ca2+ sensitivity of TRPM4. More recently, a cryo-electron microscopy structure of Ca2+-bound (but closed) TRPM4 was reported, proposing a Ca2+-binding site within an intracellular cavity formed by S2 and S3. Here, we examined the functional effects of mutations of the amino acid residues related to the proposed Ca2+-binding site on TRPM4 and also TRPM5 using mutagenesis and patch clamp techniques. The mutations of the amino acid residues of TRPM4 and TRPM5 reduced their Ca2+-sensitivities in a similar way. On the other hand, intracellular applications of PI(4,5)P2 recovered Ca2+-sensitivity of desensitized TRPM4, but its effect on TRPM5 was negligible. From these results, the Ca2+-binding sites of TRPM4 and TRPM5 were shown to be formed by the same amino acid residues by functional analyses, but the impact of PI(4,5)P2 on the regulation of TRPM5 seemed to be smaller than that on the regulation of TRPM4.
Volume 20(8)
Published 2019-4-24
DOI 10.3390/ijms20082012
PII ijms20082012
PMID 31022885
PMC PMC6514954
MeSH Amino Acid Sequence Animals Binding Sites Calcium / metabolism* HEK293 Cells Humans Male Models, Molecular Mutagenesis, Site-Directed Patch-Clamp Techniques Phosphatidylinositol 4,5-Diphosphate / metabolism* Rats TRPM Cation Channels / chemistry TRPM Cation Channels / genetics TRPM Cation Channels / metabolism*
IF 4.183
Times Cited 2
Human and Animal Cells RCB2202 : 293T