title: Investigating the Potential Signaling Pathways That Regulate Activation of the Novel PKC Downstream of Serotonin in Aplysia.
abstract: Activation of the novel PKC Apl II in sensory neurons by serotonin (5HT) underlies the ability of 5HT to reverse synaptic depression, but the pathway from 5HT to PKC Apl II activation remains unclear. Here we find no evidence for the Aplysia-specific B receptors, or for adenylate cyclase activation, to translocate fluorescently-tagged PKC Apl II. Using an anti-PKC Apl II antibody, we monitor translocation of endogenous PKC Apl II and determine the dose response for PKC Apl II translocation, both in isolated sensory neurons and sensory neurons coupled with motor neurons. Using this assay, we confirm an important role for tyrosine kinase activation in 5HT mediated PKC Apl II translocation, but rule out roles for intracellular tyrosine kinases, epidermal growth factor (EGF) receptors and Trk kinases in this response. A partial inhibition of translocation by a fibroblast growth factor (FGF)-receptor inhibitor led us to clone the Aplysia FGF receptor. Since a number of related receptors have been recently characterized, we use bioinformatics to define the relationship between these receptors and find a single FGF receptor orthologue in Aplysia. However, expression of the FGF receptor did not affect translocation or allow it in motor neurons where 5HT does not normally cause PKC Apl II translocation. These results suggest that additional receptor tyrosine kinases (RTKs) or other molecules must also be involved in translocation of PKC Apl II.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Farah
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Rourke
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Unkyung
authors.initials: U
authors.lastname: Shin
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Larissa
authors.initials: L
authors.lastname: Ferguson
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: María José
authors.initials: MJ
authors.lastname: Luna
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Wayne S
authors.identifier: http://orcid.org/0000-0003-1927-9315
authors.initials: WS
authors.lastname: Sossin
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D066246:ErbB Receptors / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010802:Phylogeny; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000145:classification / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D061987:Sf9 Cells; D015398:Signal Transduction / Q000187:drug effects*; D018411:Spodoptera; D013569:Synapses / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D017468:Receptors, Fibroblast Growth Factor; D012701:Serotonin; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D000262:Adenylyl Cyclases