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Dominant negative effects of a non-conducting TREK1 splice variant expressed in brain.

Veale, Emma L., Rees, Kathryn A., Mathie, Alistair, Trapp, Stefan (2010) Dominant negative effects of a non-conducting TREK1 splice variant expressed in brain. The Journal of biological chemistry, 285 (38). pp. 29295-304. ISSN 1083-351X. (doi:10.1074/jbc.M110.108423) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1074/jbc.M110.108423

Abstract

Two-pore domain potassium (K(2P)) channels modulate neuronal excitability throughout the entire CNS. The stretch-activated channel TREK1 (K(2P)2.1) is expressed widely in brain and has been linked to depression, neuroprotection, pain perception, and epilepsy. Little, however, is known about the regulation of TREK1 expression on the transcriptional and translational level or about its trafficking to the plasma membrane. Here we have used PCR techniques to identify a splice variant of TREK1 expressed in the brain, which encodes a heavily truncated TREK1 protein retaining a single transmembrane domain. Functional expression of this splice variant TREK1?Ex4 in tsA201 cells in the presence or absence of wild type TREK1 revealed that TREK1?Ex4 has no channel activity itself but reduced TREK1 whole cell current amplitude. Confocal analysis of the expression of fluorescently tagged TREK1 variants revealed that TREK1?Ex4 is translated, but it is retained in the intracellular compartment. Additionally, TREK1?Ex4 reduced the level of TREK1 expression in the plasma membrane. Long and short forms of TREK1 derived from alternative translation initiation are differentially affected by TREK1?Ex4, with the short form (lacking the first 41 amino acids at its N terminus) unaffected. This differential regulatory role of TREK1?Ex4 will alter the functional profile of TREK1 current in neurons where they are expressed. These results indicate that the N-terminal domain and first transmembrane domain of TREK1 are likely to be important for channel dimerization and trafficking to the plasma membrane.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M110.108423
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Alistair Mathie
Date Deposited: 12 Dec 2015 19:10 UTC
Last Modified: 29 May 2019 16:44 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53222 (The current URI for this page, for reference purposes)
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