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

✍ Scribed by Ikue Nagakura; Jake Ormond; Wayne S. Sossin

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 347 KB
• Volume: 86
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21741

✦ Synopsis

Abstract

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.