| Literature DB >> 20189104 |
Christian Grimm1, Simone Jörs, S Adrian Saldanha, Alexander G Obukhov, Bifeng Pan, Kazuo Oshima, Math P Cuajungco, Peter Chase, Peter Hodder, Stefan Heller.
Abstract
We conducted a high-throughput screen for small molecule activators of the TRPML3 ion channel, which, when mutated, causes deafness and pigmentation defects. Cheminformatics analyses of the 53 identified and confirmed compounds revealed nine different chemical scaffolds and 20 singletons. We found that agonists strongly potentiated TRPML3 activation with low extracytosolic [Na(+)]. This synergism revealed the existence of distinct and cooperative activation mechanisms and a wide dynamic range of TRPML3 activity. Testing compounds on TRPML3-expressing sensory hair cells revealed the absence of activator-responsive channels. Epidermal melanocytes showed only weak or no responses to the compounds. These results suggest that TRPML3 in native cells might be absent from the plasma membrane or that the protein is a subunit of heteromeric channels that are nonresponsive to the activators identified in this screen. Copyright 2010 Elsevier Ltd. All rights reserved.Entities:
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Year: 2010 PMID： 20189104 PMCID： PMC2834294 DOI： 10.1016/j.chembiol.2009.12.016
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521