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Cells 2018, 7(11), 218;

Emerging Roles of Diacylglycerol-Sensitive TRPC4/5 Channels

Walther Straub Institute of Pharmacology and Toxicology, Ludwig Maximilians University of Munich, 80336 Munich, Germany
DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, 80802 Munich, Germany
Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research, 81377 Munich, Germany
Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University of Munich, 80336 Munich, Germany
Authors to whom correspondence should be addressed.
Received: 30 October 2018 / Revised: 15 November 2018 / Accepted: 16 November 2018 / Published: 20 November 2018
(This article belongs to the Special Issue TRP Channels in Health and Disease)
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Transient receptor potential classical or canonical 4 (TRPC4) and TRPC5 channels are members of the classical or canonical transient receptor potential (TRPC) channel family of non-selective cation channels. TRPC4 and TRPC5 channels are widely accepted as receptor-operated cation channels that are activated in a phospholipase C-dependent manner, following the Gq/11 protein-coupled receptor activation. However, their precise activation mechanism has remained largely elusive for a long time, as the TRPC4 and TRPC5 channels were considered as being insensitive to the second messenger diacylglycerol (DAG) in contrast to the other TRPC channels. Recent findings indicate that the C-terminal interactions with the scaffolding proteins Na+/H+ exchanger regulatory factor 1 and 2 (NHERF1 and NHERF2) dynamically regulate the DAG sensitivity of the TRPC4 and TRPC5 channels. Interestingly, the C-terminal NHERF binding suppresses, while the dissociation of NHERF enables, the DAG sensitivity of the TRPC4 and TRPC5 channels. This leads to the assumption that all of the TRPC channels are DAG sensitive. The identification of the regulatory function of the NHERF proteins in the TRPC4/5-NHERF protein complex offers a new starting point to get deeper insights into the molecular basis of TRPC channel activation. Future studies will have to unravel the physiological and pathophysiological functions of this multi-protein channel complex. View Full-Text
Keywords: TRPC channels; diacylglycerol; TRPC4; TRPC5; NHERF TRPC channels; diacylglycerol; TRPC4; TRPC5; NHERF

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Mederos y Schnitzler, M.; Gudermann, T.; Storch, U. Emerging Roles of Diacylglycerol-Sensitive TRPC4/5 Channels. Cells 2018, 7, 218.

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