4.7 Review

Recent Advances in the Structural Biology of the Volume-Regulated Anion Channel LRRC8

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Pharmacology & Pharmacy

The VRAC blocker DCPIB directly gates the BK channels and increases intracellular Ca2+ in melanoma and pancreatic duct adenocarcinoma cell lines

Paolo Zuccolini et al.

Summary: This research investigated the effect of DCPIB on pancreatic duct adenocarcinoma (PDAC) and melanoma and found that DCPIB directly targeted BK channels and increased intracellular Ca2+ levels. These findings are important for the development of DCPIB-based modulators of ion channels and membrane proteins in the future.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Review Biochemistry & Molecular Biology

A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC)

Eric E. Figueroa et al.

Summary: The newly emerging roles of LRRC8 volume-regulated anion channels (VRAC) in the treatment of epilepsy, type 2 diabetes, and other human diseases raise important questions about their therapeutic potential. However, the lack of potent and specific small-molecule inhibitors and activators of VRAC hinders the evaluation of VRAC as a viable drug target. Recent progress has been made in developing the molecular pharmacology of VRAC through screening FDA-approved drugs, leading to the discovery of novel VRAC inhibitors and activators. This sets the stage for further research on the molecular pharmacology and therapeutic potential of VRAC.

CHANNELS (2022)

Article Immunology

The volume-regulated anion channel LRRC8C suppresses T cell function by regulating cyclic dinucleotide transport and STING-p53 signaling

Axel R. Concepcion et al.

Summary: LRRC8C is a critical component of VRAC in T cells, mediating the transport of 2'3' cGAMP and activating the STING-p53 signaling pathway. Its deletion enhances T cell function and increases T cell-dependent immune responses.

NATURE IMMUNOLOGY (2022)

Article Multidisciplinary Sciences

Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes

Susheel K. Gunasekar et al.

Summary: SWELL1 channel modulators represent a novel therapeutic approach for treating Type 2 diabetes and associated liver steatosis by enhancing insulin sensitivity and secretion. These modulators improve SWELL1-dependent systemic metabolism and hold promise for future treatment of diabetes and nonalcoholic fatty liver disease.

NATURE COMMUNICATIONS (2022)

Article Cell Biology

LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology

Toshiki Yamada et al.

Summary: Swelling-activated volume-regulated anion channels (VRACs) are heteromeric channels comprising LRRC8A and LRRC8 paralogs. Cryo-EM structures of LRRC8A homohexamers have limitations in mimicking VRAC function, while LRRC8A + LRRC8C heteromers exhibit strong DCPIB sensitivity that is mu dependent. The LRRC8A R103F mutation eliminates voltage dependence under low intracellular mu conditions.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2021)

Review Biochemistry & Molecular Biology

On the molecular nature of large-pore channels

Johanna Syrjanen et al.

Summary: Membrane transport plays a crucial role in controlling cellular processes, with large-pore channels serving as important conduits for ions and metabolites. These channels are formed by different protein families such as connexin, innexin, and pannexin, each contributing to diverse cellular functions.

JOURNAL OF MOLECULAR BIOLOGY (2021)

Article Multidisciplinary Sciences

Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition

Jie Yu et al.

Summary: AMPA receptors play a crucial role in mediating signal transduction in the hippocampal neuronal circuits, and their function is regulated by auxiliary protein subunits that associate with the receptors in a specific manner. Different combinations of AMPA receptor auxiliary subunits may have diverse impacts on the receptor function.

NATURE (2021)

Article Multidisciplinary Sciences

Architecture and assembly mechanism of native glycine receptors

Hongtao Zhu et al.

Summary: The study presents the cryo-electron microscopy structures of native GlyRs, revealing a predominant subunit stoichiometry of 4 alpha:1 beta and unique structural features at the beta(+)-alpha(-) interface. The presence of a phenylalanine residue in the beta-subunit disrupts the canonical picrotoxin site, impacting receptor symmetry and ion channel pharmacology. Furthermore, incomplete receptor complexes and partially assembled alpha-trimers and alpha-tetramers are identified through structural elucidation.

NATURE (2021)

Article Multidisciplinary Sciences

Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains

Dawid Deneka et al.

Summary: In this study, nanobodies targeting the LRR domain of LRRC8A have been developed and characterized, providing specific modulators for LRRC8 proteins and revealing the role of their cytoplasmic domains in regulating channel activity through allosteric mechanisms. Cryo-electron microscopy and electrophysiology experiments showed that these nanobodies can alter LRRC8A channel activity by binding to distinct epitopes of the LRR domain and changing channel conformations.

NATURE COMMUNICATIONS (2021)

Article Multidisciplinary Sciences

Cryo-EM analysis of a membrane protein embedded in the liposome

Xia Yao et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Article Biochemistry & Molecular Biology

LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP

Lauren J. Lahey et al.

MOLECULAR CELL (2020)

Article Biochemistry & Molecular Biology

DCPIB, an Inhibitor of Volume-Regulated Anion Channels, Distinctly Modulates K2P Channels

Jinyan Lv et al.

ACS CHEMICAL NEUROSCIENCE (2019)

Review Biochemistry & Molecular Biology

More than just a pressure relief valve: physiological roles of volume-regulated LRRC8 anion channels

Lingye Chen et al.

BIOLOGICAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

Membrane mimetic systems in CryoEM: keeping membrane proteins in their native environment

Henriette E. Autzen et al.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2019)

Review Physiology

Revisiting multimodal activation and channel properties of Pannexin 1

Yu-Hsin Chiu et al.

JOURNAL OF GENERAL PHYSIOLOGY (2018)

Review Biochemistry & Molecular Biology

Expression of LRRC8/VRAC Currents in Xenopus Oocytes: Advantages and Caveats

Hector Gaitan-Penas et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

Article Biochemistry & Molecular Biology

LRRC8/VRAC anion channels are required for late stages of spermatid development in mice

Jennifer C. Lueck et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Article Biochemistry & Molecular Biology

LRRC8 N termini influence pore properties and gating of volume-regulated anion channels (VRACs)

Pingzheng Zhou et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Article Multidisciplinary Sciences

LRRC8/VRAC anion channels enhance β-cell glucose sensing and insulin secretion

Till Stuhlmann et al.

NATURE COMMUNICATIONS (2018)

Article Multidisciplinary Sciences

SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia

Chen Kang et al.

NATURE COMMUNICATIONS (2018)

Article Multidisciplinary Sciences

Structure of a volume-regulated anion channel of the LRRC8 family

Dawid Deneka et al.

NATURE (2018)

Article Biochemistry & Molecular Biology

Cryo-EM structures of the human volume-regulated anion channel LRRC8

Go Kasuya et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Review Multidisciplinary Sciences

Single-particle cryo-EM-How did it get here and where will it go

Yifan Cheng

SCIENCE (2018)

Article Biology

Structure of the human volume regulated anion channel

Jennifer M. Kefauver et al.

Review Physiology

Calcium homeostasis modulator (CALHM) ion channels

Zhongming Ma et al.

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY (2016)

Article Biophysics

Investigation of LRRC8-Mediated Volume-Regulated Anion Currents in Xenopus Oocytes

Hector Gaitan-Penas et al.

BIOPHYSICAL JOURNAL (2016)

Article Biochemistry & Molecular Biology

LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength

Ruhma Syeda et al.

Review Cell Biology

VRACs and other ion channels and transporters in the regulation of cell volume and beyond

Thomas J. Jentsch

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2016)

Article Physiology

The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2

Wu Deng et al.

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY (2016)

Article Biochemistry & Molecular Biology

Deciphering key features in protein structures with the new ENDscript server

Xavier Robert et al.

NUCLEIC ACIDS RESEARCH (2014)

Article Pharmacology & Pharmacy

The inhibitor of volume-regulated anion channels DCPIB activates TREK potassium channels in cultured astrocytes

L. Minieri et al.

BRITISH JOURNAL OF PHARMACOLOGY (2013)

Article Multidisciplinary Sciences

TRPV1 structures in distinct conformations reveal activation mechanisms

Erhu Cao et al.

NATURE (2013)

Article Multidisciplinary Sciences

Structure of the TRPV1 ion channel determined by electron cryo-microscopy

Maofu Liao et al.

NATURE (2013)

Article Biochemistry & Molecular Biology

Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega

Fabian Sievers et al.

MOLECULAR SYSTEMS BIOLOGY (2011)

Review Physiology

Physiology of Cell Volume Regulation in Vertebrates

Else K. Hoffmann et al.

PHYSIOLOGICAL REVIEWS (2009)

Review Biochemical Research Methods

RECONSTITUTION OF MEMBRANE PROTEINS IN PHOSPHOLIPID BILAYER NANODISCS

T. K. Ritchie et al.

METHODS IN ENZYMOLOGY; LIPOSOMES, PT F (2009)