TRPV5

Last update 23 Jan 2025

Basic Info

Synonyms

Calcium transport protein 2, CaT2, ECaC

+ [7]

Introduction

Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:11549322, PubMed:18768590). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (PubMed:11549322, PubMed:18768590). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).

100 Clinical Results associated with TRPV5

100 Translational Medicine associated with TRPV5

0 Patents (Medical) associated with TRPV5

562

Literatures (Medical) associated with TRPV5

02 Jan 2025·Current Topics in Medicinal Chemistry

Advances in the Study for Modulators of Transient Receptor Potential Vanilloid (TRPV) Channel Family

Article

Author: Zuo, Minmin ; Yu, Yingcong ; Wang, Yajing ; Shi, Yingying ; Huang, Xianfeng

Abstract:Transient receptor potential vanilloid (TRPV) channels are a member of the TRP superfamily, which consists of six proteins and is expressed in many neuronal and non-neuronal cells. Among them, TRPV1-4 are non-selective cation channels that are highly sensitive to temperature changes, while TRPV5-6 are channels that are highly selective to Ca2+. These cation channels have attracted great interest academically, especially from a pharmacological perspective. TRPV channels play a vital role in many physiological processes and can be regulated by a variety of endogenous stimuli as well as a range of natural and synthetic compounds. The regulation of their activities can lead to a variety of diseases and disorders, such as neurodegenerative diseases, pain, cancer, and skin diseases. In fact, several TRPV1 and TRPV3 modulators have been developed for clinical use. Therefore, the development of TRPV channel modulators has important clinical significance and value. Herein, we focused on and summarized the latest research progress of endogenous and exogenous ligands of six TRPV channels and their pharmacological effects on related diseases.

01 Dec 2024·Current Urology Reports

Role of Genetic Testing in Kidney Stone Disease: A Narrative Review

Review

Author: Lovegrove, Catherine ; Howles, Sarah ; Geraghty, Robert ; Sayer, John A

AbstractPurpose of ReviewKidney stone disease (KSD) is a common and potentially life-threatening condition, and half of patients experience a repeat kidney stone episode within 5–10 years. Despite the ~50% estimate heritability of KSD, international guidelines have not kept up with the pace of discovery of genetic causes of KSD. The European Association of Urology guidelines lists 7 genetic causes of KSD as ‘high risk’.Recent FindingsThere are currently 46 known monogenic (single gene) causes of kidney stone disease, with evidence of association in a further 23 genes. There is also evidence for polygenic risk of developing KSD. Evidence is lacking for recurrent disease, and only one genome wide association study has investigated this phenomenon, identifying two associated genes (SLC34A1 and TRPV5). However, in the absence of other evidence, patients with genetic predisposition to KSD should be treated as ‘high risk’. Further studies are needed to characterize both monogenic and polygenic associations with recurrent disease, to allow for appropriate risk stratification. Durability of test result must be balanced against cost. This would enable retrospective analysis if no genetic cause was found initially.SummaryWe recommend genetic testing using a gene panel for all children, adults < 25 years, and older patients who have factors associated with high risk disease within the context of a wider metabolic evaluation. Those with a genetic predisposition should be managed via a multi-disciplinary team approach including urologists, radiologists, nephrologists, clinical geneticists and chemical pathologists. This will enable appropriate follow-up, counselling and potentially prophylaxis.

01 Dec 2024·The Journal of Physiology

Calmodulin regulates TRPV5 intracellular trafficking and plasma membrane abundance

Article

Author: van de Langenberg, Brenda ; Witte, Guusje ; Grigore, Teodora ; van der Wijst, Jenny ; Zuidscherwoude, Malou ; Hoenderop, Joost G.

AbstractAs a member of the transient receptor potential (TRP) superfamily of ion channels, TRPV5 is a unique Ca2+‐selective channel important for active reabsorption of Ca2+ in the kidney. TRPV5‐mediated Ca2+ entry into the cell is controlled by a negative feedback mechanism, in which calmodulin (CaM) blocks the TRPV5 pore upon Ca2+ binding. Combining microscopy techniques and biochemical assays, the present study uncovered an auxiliary role for CaM in the regulation of human (h)TRPV5 intracellular trafficking. Overexpressed hTRPV5 was mainly localised to the endoplasmic reticulum (ER) and associated with peripheral ER tubules. Limiting expression using the HEK293 TET‐off system revealed that hTRPV5 trafficked through the endocytic recycling pathway. CaM co‐localised with hTRPV5 at intracellular sites and overexpression of CaM slowed hTRPV5 exit from the ER. In accordance, CaM binding‐disrupting truncations of the TRPV5 C‐terminus (698X) or knockdown of endogenous CaM by small interfering RNA resulted in an increased fraction of TRPV5 that localised to the plasma membrane. hTRPV5 expressing cells had an increased intracellular Ca2+ concentration upon knockdown of CaM. The protein abundance of the Ca2+ impermeable hTRPV5‐D542 mutant is also regulated by CaM, which suggests that the mode of action is independent of disrupted intracellular calcium concentrations. In conclusion, our study reveals a novel role for CaM in Ca2+‐dependent TRPV5 regulation, modulating TRPV5 intracellular trafficking.

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Key points

The renal Ca2+ channel TRPV5 is a crucial player in maintenance of the body's Ca2+ homeostasis.

Ca2+ transport through TRPV5 is controlled by single channel activity, as well as TRPV5 plasma membrane abundance.

Calmodulin (CaM) co‐localised with TRPV5 at intracellular sites and retained TRPV5 in the endoplasmic reticulum.

Disrupted CaM–TRPV5 binding or knockdown of endogenous CaM by small interfering RNA (siRNA) resulted in an increased TRPV5 plasma membrane abundance.

Knockdown of endogenous CaM by siRNA resulted in increased intracellular Ca2+ concentrations. The regulation of TRPV5 trafficking by CaM is independent of the effect of CaM on intracellular Ca2+ concentrations.

This study reveals a novel role for CaM in Ca2+‐dependent TRPV5 regulation, next to its ability to directly block the TRPV5 channel pore, by modulating TRPV5 trafficking in the secretory pathway.

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TRPV5

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