Mechanisms regulating ApTrkl, a Trk-like receptor in Aplysia sensory neurons.

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. (c) 2008 Wiley-Liss, Inc.