title: Teneurins, TCAP, and latrophilins: roles in the etiology of mood disorders.
abstract: Mood disorders, including anxiety and depression, are thought to be characterized by disrupted neuronal synapses and altered brain plasticity. The etiology is complex, involving numerous regions of the brain, comprising a multitude of neurotransmitter and neuromodulator systems. Recently, new studies on the teneurins, an evolutionary ancient family of type II transmembrane proteins have been shown to interact with latrophilins (LPHN), a similarly phylogenetically old family of adhesion G protein-coupled receptors (GPCR) forming a transsynaptic adhesion and ligand-receptor pair. Each of the four teneurin proteins contains bioactive sequences termed the teneurin C-terminal associated peptides (TCAP-1-4), which possess a number of neuromodulatory effects. The primary structures of the TCAP are most closely similar to the corticotropin-releasing factor (CRF) family of peptides. CRF has been implicated in a number of diverse mood disorders. Via an association with dystroglycans, synthetic TCAP-1 administration to both embryonic and primary hippocampal cultures induces long-term changes in neuronal structure, specifically increased neurite outgrowth, dendritic branching, and axon growth. Rodent models treated with TCAP-1 show reduced anxiety responses in the elevated plus-maze, openfield test, and acoustic startle test and inhibited CRF-mediated cocaine-seeking behaviour. Thus the teneurin/TCAP-latrophilin interaction may play a major role in the origin, development and treatment of mood disorders.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Woelfle
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: D'Aquila
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Lovejoy
keywords: Addiction; Anxiety; Corticotropin-releasing factor; Neuromodulation; Secretin peptide family; Stress; Synaptic plasticity