Free fatty acid receptor 4 agonists induce lysophosphatidic acid receptor 1 (LPA 1 ) desensitization independent of LPA 1 internalization and heterodimerization

The crosstalk between the free fatty acid receptor FFA4 and the lysophosphatidic acid receptor LPA seems to be of pathophysiological importance. We explored this crosstalk employing co-expression of fluorescent protein-tagged receptors. FFA4 activation induces functional desensitization of LPA recep...

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Bibliographic Details
Published in:FEBS letters 2018-08, Vol.592 (15), p.2612-2623
Main Authors: Meizoso-Huesca, Aldo, Villegas-Comonfort, Sócrates, Romero-Ávila, M Teresa, García-Sáinz, J Adolfo
Format: Article
Language:English
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Summary:The crosstalk between the free fatty acid receptor FFA4 and the lysophosphatidic acid receptor LPA seems to be of pathophysiological importance. We explored this crosstalk employing co-expression of fluorescent protein-tagged receptors. FFA4 activation induces functional desensitization of LPA receptors and phosphorylation of both receptors. LPA activation induces phosphorylation of LPA , but not of FFA4, and induces internalization of both receptors into heterogeneous types of vesicles. Docosahexaenoic acid (DHA) induces internalization of FFA4 but not of LPA . Fatty acid-induced FFA4-LPA interaction was observed using Förster resonance energy transfer and co-immunoprecipitation. Such interaction took place after desensitization was already established. Data indicate that FFA4 activation induces LPA desensitization in an internalization-independent process and that complex cellular processes participate in the crosstalk of these receptors.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.13179