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| http://dx.doi.org/10.1085/jgp.201611686 | DOI Listing |
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Distinct modulation of calcium-activated chloride channel TMEM16A by drug-binding sites.
Proc Natl Acad Sci U S A
December 2024
Channelopathy Research Center, Dongguk University College of Medicine, Goyang 10326, Republic of Korea.
Article Synopsis
- * Using magnolol and honokiol, researchers identified two distinct drug-binding sites on TMEM16A—one in the pore region and another nonpore pocket, each interacting differently with the channel.
- * The study highlights that out of 17 inhibitors tested, a majority acted as pore blockers, revealing the significance of the nonpore pocket and informing future drug development strategies.
TMEM16 proteins: Ca‑activated chloride channels and phospholipid scramblases as potential drug targets (Review).
Int J Mol Med
October 2024
Department of Hand and Foot Surgery, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University), Shenzhen, Guangdong 518000, P.R. China.
TMEM16 proteins, which function as Ca‑activated Cl channels are involved in regulating a wide variety of cellular pathways and functions. The modulators of Cl channels can be used for the molecule‑based treatment of respiratory diseases, cystic fibrosis, tumors, cancer, osteoporosis and coronavirus disease 2019. The TMEM16 proteins link Ca signaling, cellular electrical activity and lipid transport.
View Article and Find Full Text PDFModulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells.
J Biol Chem
July 2024
Center for the Investigation of Membrane Excitability Diseases (CIMED), Washington University School of Medicine, Saint Louis, Missouri, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, Missouri, USA; Division of Pulmonary and Critical Care, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Saint Louis, Missouri, USA. Electronic address:
The Ca-activated Cl channel regulator CLCA1 potentiates the activity of the Ca-activated Cl channel (CaCC) TMEM16A by directly engaging the channel at the cell surface, inhibiting its reinternalization and increasing Ca-dependent Cl current (I) density. We now present evidence of functional pairing between two other CLCA and TMEM16 protein family members, namely CLCA4 and the CaCC TMEM16B. Similar to CLCA1, (i) CLCA4 is a self-cleaving metalloprotease, and the N-terminal portion (N-CLCA4) is secreted; (ii) the von Willebrand factor type A (VWA) domain in N-CLCA4 is sufficient to potentiate I in HEK293T cells; and (iii) this is mediated by the metal ion-dependent adhesion site motif within VWA.
View Article and Find Full Text PDFInteraction between TRP channels and anoctamins.
Cell Calcium
July 2024
Division of Cell Signaling, National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Aza-Higashiyama, Myodaiji, Okazaki, Aichi, Japan; Thermal Biology Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, 5-1 Aza-Higashiyama, Myodaiji, Okazaki, Aichi, Japan; Thermal Biology Research Group, Nagoya Advanced Research and Development Center, Nagoya City University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, Japan. Electronic address:
Article Synopsis
- * TRP channels are crucial non-selective cation channels involved in various physiological functions across different body tissues, with significant research beginning after the discovery of TRPV1 in 1997.
- * The review focuses on recent insights into how ANO1 interacts with specific TRP channels (like TRPV4, TRPC6, TRPV3, TRPV1, and TRPC2) in multiple tissues, indicating that ANO1 may regulate functions via chloride ion movement in those areas.
Ca-Dependent Cl Channels in Vascular Tone Regulation during Aging.
Int J Mol Sci
May 2024
Faculty of Medicine, Institute of Pharmacology and Clinical Pharmacology, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.
Article Synopsis
- Identifying aging-related changes in vascular tone is crucial for improving cardiovascular disease diagnosis, as various mechanisms like NO synthase activity and sympathetic nervous system activity play roles in this regulation.
- Calcium-dependent chloride channels (CaCCs) significantly affect all aspects of vascular tone regulation, and their activation is linked to both intracellular calcium levels and voltage, which fine-tunes vascular response.
- As individuals age, there's a decline in CaCC activation due to reduced protein levels and impaired calcium influx, which may contribute to the overall alterations in vascular tone regulation.
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