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Mechanisms regulating ApTrkl, a Trk‐like receptor in Aplysia sensory neurons
Author(s) -
Nagakura Ikue,
Ormond Jake,
Sossin Wayne S.
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21741
Subject(s) - internalization , microbiology and biotechnology , g protein coupled receptor , biology , receptor , inverse agonist , aplysia , tropomyosin receptor kinase c , agonist , endogenous agonist , receptor tyrosine kinase , neuroscience , signal transduction , biochemistry , platelet derived growth factor receptor , growth factor , dopamine receptor d1
An Aplysia Trk‐like receptor (ApTrkl) was previously shown to be involved in cell wide long‐term facilitation (LTF) and activation of ERK when serotonin (5‐HT) is applied to the cell soma. The current study investigated the regulation of ApTrkl by overexpressing the receptor and several variants in Aplysia sensory neuron cultures. Kinase activity–dependent constitutive activation of ApTrkl was observed mainly on the plasma membrane. These studies revealed two modes of receptor internalization: (1) kinase activity–dependent internalization and (2) 5‐HT‐dependent, kinase activity–independent internalization. Both modes of internalization were ligand independent, and the action of 5‐HT was mediated through G‐protein‐coupled receptors (GPCRs). On the other hand, methiothepin, an inverse agonist of 5‐HT GPCRs activated endogenous ApTrkl to the same extent as 5‐HT, suggesting a transactivation mechanism due to a novel coupling of GPCRs to receptor tyrosine kinase (RTK) activation that is also activated through inverse agonist binding. The neuropeptide sensorin could transiently activate ApTrkl but was not required for 5‐HT‐induced ApTrkl activation. © 2008 Wiley‐Liss, Inc.