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.
Nagakura
Ikue
I
Department of Psychology, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada.
Ormond
Jake
J
Sossin
Wayne S
WS
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology*; D007150:Immunohistochemistry; D021381:Protein Transport / Q000502:physiology; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015533:Transcriptional Activation
D043562:Receptors, G-Protein-Coupled; D012701:Serotonin; D020917:Receptor, trkA