Document Detail


Proton conductivity through the human TRPM7 channel and its molecular determinants.
MedLine Citation:
PMID:  18390554     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TRPM7 is a divalent cation-permeable channel that is ubiquitously expressed. Recently, mouse TRPM7 has been shown to be sensitive to, and even permeable to, protons when heterologously expressed. Here we have demonstrated that human TRPM7 expressed either heterologously or endogenously also exhibits proton conductivity. The gene silencing of TRPM7 by small interfering RNA suppressed H+ currents in human cervical epithelial HeLa cells. In HEK293T cells transfected with human TRPM7, the inward proton conductance was suppressed by extracellular Mg2+ or Ca2+ with IC(50) values of 0.5 and 1.9 mm, respectively. Anomalous mole fraction behavior of H+ currents in the presence of Mg2+ or Ca2+ indicated that these divalent cations compete with protons for binding sites. Systematic mutation of negatively charged amino acid residues within the putative pore-forming region of human TRPM7 into the neutral amino acid alanine was tested. E1047A resulted in non-functional channels, and D1054A abolished proton conductance, whereas E1052A and D1059A only partially reduced proton conductivity. Thus, it is concluded that Asp-1054 is an essential determinant of the proton conductivity, whereas Glu-1047 might be required for channel formation, and the remaining negatively charged amino acids in the pore region (Glu-1052 and Asp-1059) may play a facilitating role in the proton conductivity of human TRPM7. It is suggested that proton conductivity of endogenous human TRPM7 plays a role in physiologically/pathologically acidic situations.
Authors:
Tomohiro Numata; Yasunobu Okada
Related Documents :
17940284 - The leader peptide of yeast atp6p is required for efficient interaction with the atp9p ...
18412544 - An amino acid at position 142 in nitrilase from rhodococcus rhodochrous atcc 33278 dete...
21744274 - Enantioselective esterification of (r,s)-2-methylalkanoic acid with carica papaya lipas...
16531464 - Interactions between jasmonates and ethylene in the regulation of root hair development...
7451494 - The chemical labeling of glutamate decarboxylase in vivo.
16833484 - Hard-soft acid-base interactions of silylenes and germylenes.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-05-26     Completed Date:  2008-07-17     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15097-103     Citation Subset:  IM    
Affiliation:
Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
Binding Sites / physiology
Calcium / metabolism
Cations, Divalent / metabolism
Gene Silencing
HeLa Cells
Humans
Ion Transport / physiology
Magnesium / metabolism
Mice
Protons*
RNA, Small Interfering
TRPM Cation Channels / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Cations, Divalent; 0/Protons; 0/RNA, Small Interfering; 0/TRPM Cation Channels; 7439-95-4/Magnesium; 7440-70-2/Calcium; EC 2.7.1.-/TRPM7 protein, human; EC 2.7.1.-/Trpm7 protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Novel splice variants of rat CaV2.1 that lack much of the synaptic protein interaction site are expr...
Next Document:  Identification of a novel chondroitin hydrolase in Caenorhabditis elegans.