title: Ancient interaction between the teneurin C-terminal associated peptides (TCAP) and latrophilin ligand-receptor coupling: a role in behavior.
abstract: Teneurins are multifunctional transmembrane proteins that are found in all multicellular animals and exist as four paralogous forms in vertebrates. They are highly expressed in the central nervous system, where they exert their effects, in part, by high-affinity binding to latrophilin (LPHN), a G-protein coupled receptor (GPCR) related to the adhesion and secretin GPCR families. The teneurin C-terminal associated peptides (TCAPs) are encoded by the terminal exon of all four teneurins, where TCAPs 1 and 3 are independently transcribed as soluble peptides, and TCAPs 2 and 4 remain tethered to their teneurin proprotein. Synthetic TCAP-1 interacts with LPHN, with an association with β-dystroglycan, to induce a tissue-dependent signal cascade to modulate cytoskeletal dynamics. TCAP-1 reduces stress-induced behaviors associated with anxiety, addiction and depression in a variety of models, in part, by regulating synaptic plasticity. Therefore, the TCAP-1-teneurin-LPHN interaction represents a novel receptor-ligand model and may represent a key mechanism underlying the association of behavior and neurological conditions.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Woelfle
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: D'Aquila
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada.
authors.forename: Téa
authors.initials: T
authors.lastname: Pavlović
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada.
authors.forename: Mia
authors.initials: M
authors.lastname: Husić
authors.affiliation: Department of Cell and Systems Biology, University of Toronto Toronto, ON, Canada ; Protagenic Therapeutics Inc. New York, NY, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Lovejoy
keywords: adhesion GPCR; molecular evolution; neuroendocrine interactions; stress; synapse