Structural basis of TRPV5 regulation by physiological and pathophysiological modulators

Fluck, Edwin C.; Yazici, Aysenur; Rohács, Tibor; Moiseenkova-Bell, Vera Y.

doi:10.1016/j.celrep.2022.110737

Cited by 33 publications

(15 citation statements)

References 56 publications

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“…Since PTH may act via both, intracellular cAMP or Ca 2+ release, 34,47,48 exact mechanisms that trigger PMCA and TRPV5 stimulation in response to furosemide remain to be clarified. In addition, chronic furosemide administration may further affect TRPV5 activity by modulation of the urinary pH 49,50 …”

Section: Discussionmentioning

confidence: 99%

Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model

et al. 2023

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Aim: Perturbed calcium homeostasis limits life expectancy in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). This rare disease occurs by loss-of-function mutations in CLDN16 or CLDN19 genes, causing impaired paracellular reabsorption of divalent cations along the cortical thick ascending limb (cTAL). Only partial compensation takes place in the ensuing late distal convoluted tubule, connecting tubule, and collecting duct, where the luminal transient receptor potential channel V5 (TRPV5), as well as basolateral plasma membrane calcium ATPase (PMCA) and sodium-potassium exchanger (NCX1) mediate transcellular Ca 2+ reabsorption. The loop diuretic furosemide induces compensatory activation in these distal segments. Normally, furosemide enhances urinary calcium excretion via inhibition of the aforementioned cTAL.

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Section: Discussionmentioning

confidence: 99%

Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model

et al. 2023

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“…In this work, all simulations were performed with the GROMACS 5.1.2 package. 32 The cryo-electron microscopy structure of TRPV5 at pH8 in nanodiscs (PDB code: 7T6J), 33 which represents a closed conformation, was employed for the subsequent CG modeling and simulation. In the Martini model, the Lennard-Jones potential function is used to describe the van der Waals interactions, while charged CG particles interact through the Coulomb energy function.…”

Section: Methodsmentioning

confidence: 99%

Probing Conformational Transition of TRPV5 Induced by Mechanical Force Using Coarse-Grained Molecular Dynamics

Gu,

Li,

et al. 2023

J. Chem. Inf. Model.

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Transient receptor potential vanilloid 5 (TRPV5) is a calcium-selective TRP channel that plays a crucial role in calcium homeostasis regulation. However, there are still many issues that need to be addressed, such as the specific conformational transition of TRPV5 and the specific functions of each structure in cation gating. Here, we build a model of the calcium ion transport protein from Xenopus oocytes in the presence of the lipid membrane and water molecules. Due to the activation process of ion channels are global and collective, coarse-grained molecular dynamics (CG-MD) simulations of the potential of mean force along the conformational transition pathway are performed. The CG-MD simulations show that the S6 helix plays a vital role in the TRPV5 conformational transition. Most importantly, these simulated trajectories indicate that the activation of ion channels happens before the extension and rotation of S6 helices, revealing that TRPV5 has a unique gating mechanism different from TRPV6. The present work demonstrates how the mechanical force acting on the S6 helix opens the TRPV5 channel gates. These results deepen our understanding of the TRPV5 gating mechanism.

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“…As discussed earlier, the primary role of TRPV5 involves mediating Ca 2+ uptake and transport. Research has demonstrated the indispensability of TRPV5 in epithelial calcium uptake, bone formation, and the regulation of calcium homeostasis, particularly in renal calcium reabsorption, with particular emphasis on renal calcium reabsorption and its intimate connection to bone homeostasis [ 15 , 109 , 110 ]. Notably, TRPV5 functions differently from TRPV1-4, as it is not activated by ligands and is unrelated to the thermosensitive channel family [ 111 ].…”

Section: Overview Of Trpv5mentioning

confidence: 99%

“…Furthermore, other pathways for the inhibition of TRPV5 activity under acidic conditions have been reported. Edwin C. Fluck et al [ 110 ] found that the activation of PI (4,5) P 2 was prevented under low pH conditions to suppress TRPV5 activity, revealing a synergistic effect of pH and lipid co-factor in gating the channel. The transition of TRPV5 channel from open to closed conformation under low pH environment was captured using cryo-electron microscopy.…”

Section: Overview Of Trpv5mentioning

confidence: 99%

Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis

Luo

Zhang

et al. 2023

J Transl Med

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The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

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Structural basis of TRPV5 regulation by physiological and pathophysiological modulators

Cited by 33 publications

References 56 publications

Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model

Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model

Probing Conformational Transition of TRPV5 Induced by Mechanical Force Using Coarse-Grained Molecular Dynamics

Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis

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