title: A novel fibroblast growth factor receptor family member promotes neuronal outgrowth and synaptic plasticity in aplysia.
abstract: Fibroblast Growth Factor (FGF) Receptors (FGFRs) regulate essential biological processes, including embryogenesis, angiogenesis, cellular growth and memory-related long-term synaptic plasticity. Whereas canonical FGFRs depend exclusively on extracellular Immunoglobulin (Ig)-like domains for ligand binding, other receptor types, including members of the tropomyosin-receptor-kinase (Trk) family, use either Ig-like or Leucine-Rich Repeat (LRR) motifs, or both. Little is known, however, about the evolutionary events leading to the differential incorporation of LRR domains into Ig-containing tyrosine kinase receptors. Moreover, although FGFRs have been identified in many vertebrate species, few reports describe their existence in invertebrates. Information about the biological relevance of invertebrate FGFRs and evolutionary divergences between them and their vertebrate counterparts is therefore limited. Here, we characterized ApLRRTK, a neuronal cell-surface protein recently identified in Aplysia. We unveiled ApLRRTK as the first member of the FGFRs family deprived of Ig-like domains that instead contains extracellular LRR domains. We describe that ApLRRTK exhibits properties typical of canonical vertebrate FGFRs, including promotion of FGF activity, enhancement of neuritic outgrowth and signaling via MAPK and the transcription factor CREB. ApLRRTK also enhanced the synaptic efficiency of neurons known to mediate in vivo memory-related defensive behaviors. These data reveal a novel molecular regulator of neuronal function in invertebrates, provide the first evolutionary linkage between LRR proteins and FGFRs and unveil an unprecedented mechanism of FGFR gene diversification in primeval central nervous systems.
authors: Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Center for Physiology and Pharmacology, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors: Daniela D
authors: DD
authors: Pollak
authors: Bui Quang
authors: BQ
authors: Minh
authors: Ana
authors: A
authors: Cicvaric
authors: Francisco J
authors: FJ
authors: Monje
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019143:Evolution, Molecular; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012701:Serotonin / Q000737:chemistry; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D017468:Receptors, Fibroblast Growth Factor; D012701:Serotonin; D020794:Receptor Protein-Tyrosine Kinases