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A novel ion channel formed by interaction of TRPML3 with TRPV5.

Guo Z, Grimm C, Becker L, Ricci AJ, Heller S - PLoS ONE (2013)

Bottom Line: It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5.Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations.Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-HNS, Stanford University School of Medicine, Palo Alto, California, United States of America.

ABSTRACT
TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.

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Single channel recordings of TRPV5, TRPML3, and TRPML3/TRPV5 currents.Shown are representative single-channel traces, as well as amplitude and open dwell-time histograms for TRPV5 (A), TRPML3 (B), and the two varieties of traces observed for TRPML3/TRPV5 (C,D) under conditions 1, 2, and 3 at −150 mV. Solid lines and dotted lines represent closed and open averaged, respectively. The open dwell-time histograms were fitted to biexponential functions.
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pone-0058174-g006: Single channel recordings of TRPV5, TRPML3, and TRPML3/TRPV5 currents.Shown are representative single-channel traces, as well as amplitude and open dwell-time histograms for TRPV5 (A), TRPML3 (B), and the two varieties of traces observed for TRPML3/TRPV5 (C,D) under conditions 1, 2, and 3 at −150 mV. Solid lines and dotted lines represent closed and open averaged, respectively. The open dwell-time histograms were fitted to biexponential functions.

Mentions: Single channel analyses in outside-out patches from plasmid-transfected HEK293 cells revealed obvious differences among TRPV5, TRPML3, and the novel conductance. TRPV5 was not active under conditions 1 and 2, but under condition 3 at −150 mV, it displayed relatively large single channel events with a conductance of 105.27±5.4 pS (n = 6) and average open times of 1.02±0.12 ms (Fig. 6A). This single channel behavior is in agreement with previous reports [27], [28]. TRPML3 also showed expected behavior and was only active under conditions 2 and 4, with an average conductance under condition 2 of 32.7±1.0 pS at −150 mV, and an average open time of 0.22±0.06 ms (n = 5) (Fig. 6B).


A novel ion channel formed by interaction of TRPML3 with TRPV5.

Guo Z, Grimm C, Becker L, Ricci AJ, Heller S - PLoS ONE (2013)

Single channel recordings of TRPV5, TRPML3, and TRPML3/TRPV5 currents.Shown are representative single-channel traces, as well as amplitude and open dwell-time histograms for TRPV5 (A), TRPML3 (B), and the two varieties of traces observed for TRPML3/TRPV5 (C,D) under conditions 1, 2, and 3 at −150 mV. Solid lines and dotted lines represent closed and open averaged, respectively. The open dwell-time histograms were fitted to biexponential functions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585263&req=5

pone-0058174-g006: Single channel recordings of TRPV5, TRPML3, and TRPML3/TRPV5 currents.Shown are representative single-channel traces, as well as amplitude and open dwell-time histograms for TRPV5 (A), TRPML3 (B), and the two varieties of traces observed for TRPML3/TRPV5 (C,D) under conditions 1, 2, and 3 at −150 mV. Solid lines and dotted lines represent closed and open averaged, respectively. The open dwell-time histograms were fitted to biexponential functions.
Mentions: Single channel analyses in outside-out patches from plasmid-transfected HEK293 cells revealed obvious differences among TRPV5, TRPML3, and the novel conductance. TRPV5 was not active under conditions 1 and 2, but under condition 3 at −150 mV, it displayed relatively large single channel events with a conductance of 105.27±5.4 pS (n = 6) and average open times of 1.02±0.12 ms (Fig. 6A). This single channel behavior is in agreement with previous reports [27], [28]. TRPML3 also showed expected behavior and was only active under conditions 2 and 4, with an average conductance under condition 2 of 32.7±1.0 pS at −150 mV, and an average open time of 0.22±0.06 ms (n = 5) (Fig. 6B).

Bottom Line: It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5.Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations.Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology-HNS, Stanford University School of Medicine, Palo Alto, California, United States of America.

ABSTRACT
TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.

Show MeSH
Related in: MedlinePlus