From worm to man: three subfamilies of TRP channels

Harteneck, Christian; Plant, Tim; Schultz, Günter

doi:10.1016/s0166-2236(99)01532-5

Cited by 453 publications

(302 citation statements)

References 63 publications

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“…Based on their sequence similarity to voltage-gated ion channels, TRPs are likely to form tetramers (12). Our x-ray crystallography studies indicate that two kinase domains of TRPM7 associate as a domain-swapped dimer.…”

Section: Discussionmentioning

confidence: 83%

“…Based on revised nomenclature for TRP channels, the kinasecontaining TRP has been termed TRPM7/ChaK1 based on its similarity to long TRP family members, melastatin, MTR1 (TRPM5), and LTRPC2 (TRPM2) (7). A closely related gene, TRPM6/ChaK2 has also been identified as being mutated in familial hypomagnesemia (8, 9), and a key role for both TRPM6 and TRPM7 has been suggested in Mg 2ϩ homeostasis (8 -11).Members of the TRP family of channels contain six predicted transmembrane segments and are related to the superfamily of ion channels that include voltage-gated K ϩ channels and cyclic nucleotide-gated channels (12,13). In addition to the kinase domain at the C terminus of TRPM7, other regions of potential functional importance are a putative coiled-coil domain and a domain enriched in Ser/Pro and Thr/Pro motifs (the STP domain) (Fig.…”

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confidence: 99%

“…Members of the TRP family of channels contain six predicted transmembrane segments and are related to the superfamily of ion channels that include voltage-gated K ϩ channels and cyclic nucleotide-gated channels (12,13). In addition to the kinase domain at the C terminus of TRPM7, other regions of potential functional importance are a putative coiled-coil domain and a domain enriched in Ser/Pro and Thr/Pro motifs (the STP domain) (Fig.…”

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confidence: 99%

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Channel Function Is Dissociated from the Intrinsic Kinase Activity and Autophosphorylation of TRPM7/ChaK1

Matsushita

Kozak

Shimizu³

et al. 2005

Journal of Biological Chemistry

178

213

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TRPM7/ChaK1 is a unique channel/kinase that contains a TRPM channel domain with 6 transmembrane segments fused to a novel serine-threonine kinase domain at its C terminus. The goal of this study was to investigate a possible role of kinase activity and autophosphorylation in regulation of channel activity of TRPM7/ChaK1. Residues essential for kinase activity were identified by site-directed mutagenesis. Two major sites of autophosphorylation were identified in vitro by mass spectrometry at Ser 1511 and Ser 1567 , and these sites were found to be phosphorylated in intact cells. TRPM7/ ChaK1 is a cation-selective channel that exhibits strong outward rectification and inhibition by millimolar levels of internal [Mg 2؉ ]. Mutation of the two autophosphorylation sites or of a key catalytic site that abolished kinase activity did not alter channel activity measured by whole-cell recording or Ca 2؉ influx. Inhibition by internal Mg 2؉ was also unaffected in the autophosphorylation site or "kinase-dead" mutants. Moreover, kinase activity was enhanced by Mg 2؉ , was decreased by Zn 2؉ , and was unaffected by Ca 2؉ . In contrast, channel activity was inhibited by all three of these divalent cations. However, deletion of much of C-terminal kinase domain resulted in expression of an apparently inactive channel. We conclude that neither current activity nor regulation by internal Mg 2؉ is affected by kinase activity or autophosphorylation but that the kinase domain may play a structural role in channel assembly or subcellular localization.Recent studies have characterized several unique protein kinases that display no amino acid sequence similarity to the superfamily of protein kinase A-related enzymes, including eukaryotic elongation factor-2 kinase (EF2K) 1 and Dictyostelium myosin heavy chain kinases A, B, and C (MHCK A-C). Several additional catalytic domains related to EF2K and MHCK have been identified through data base searches in mammals as well as in nematode worm, although the function of these potential protein kinases is not known (1-3). Using this approach, we and others identified an 1863-amino acid polypeptide (termed ChaK for channel kinase) that contained a TRP-related channel domain fused to the atypical kinase domain at its C terminus (3, 4). The same gene product was also identified in a yeast two-hybrid screen using a portion of phospholipase C ␤1 as bait (and termed TRP-PLIK) (5) and in a screen for TRP-related channels (and termed LTRPC7) (6). Based on revised nomenclature for TRP channels, the kinasecontaining TRP has been termed TRPM7/ChaK1 based on its similarity to long TRP family members, melastatin, MTR1 (TRPM5), and LTRPC2 (TRPM2) (7). A closely related gene, TRPM6/ChaK2 has also been identified as being mutated in familial hypomagnesemia (8, 9), and a key role for both TRPM6 and TRPM7 has been suggested in Mg 2ϩ homeostasis (8 -11).Members of the TRP family of channels contain six predicted transmembrane segments and are related to the superfamily of ion channels that include voltage-gated K ϩ...

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Section: Discussionmentioning

confidence: 83%

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confidence: 99%

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confidence: 99%

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Channel Function Is Dissociated from the Intrinsic Kinase Activity and Autophosphorylation of TRPM7/ChaK1

Matsushita

Kozak

Shimizu³

et al. 2005

Journal of Biological Chemistry

178

213

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“…TRPV5 and TRPV6 constitute a distinct class of highly Ca 2+ -selective channels within the transient receptor potential (TRP) superfamily, which encompasses a diversity of non-voltage operated cation channels (Clapham et al 2001;Harteneck et al 2000;Montell et al 2002b). These two channels belong to the TRPV (vanilloid) subfamily, which is one of the subfamilies comprising this su-perfamily (Hoenderop et al 2005;Montell et al 2002a;Peng et al 2003;Vennekens et al 2002).…”

Section: Molecular Features Of Trpv5 and Trpv6mentioning

confidence: 99%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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The epithelial Ca 2+ channels TRPV5 and TRPV6 represent a new family of Ca 2+ channels that belongs to the superfamily of transient receptor potential channels. TRPV5 and TRPV6 constitute the apical Ca 2+ entry mechanism in active Ca 2+ transport in kidney and intestine. The central role of TRPV5 and TRPV6 in active Ca 2+ (re)absorption makes it a prime target for regulation to maintain Ca 2+ balance. This review covers the hormonal regulation, interaction with accessory proteins and (patho)physiological implications of these epithelial Ca 2+ channels.

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“…Recently, a transient receptor potential (TRP) protein superfamily was identified, consisting of a diverse group of calcium-permeable cation channels expressed in nonexcitable cells, based on the archetypal TRP cloned in Drosophila (21,22). Drosophila TRP is predominantly expressed in the visual system, is required for phototransduction, and is coupled via a G protein to phospholipase C. Based on sequences from Drosophila TRP, a large number of mammalian isoforms have been cloned, which have been divided into six subfamilies (22).…”

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confidence: 99%