Abstract
The adhesion G protein-coupled receptors latrophilins have been in the limelight for more than 20 years since their discovery as calcium-independent receptors for α-latrotoxin, a spider venom toxin with potent activity directed at neurotransmitter release from a variety of synapse types. Latrophilins are highly expressed in the nervous system. Although a substantial amount of studies has been conducted to describe the role of latrophilins in the toxin-mediated action, the recent identification of endogenous ligands for these receptors helped confirm their function as mediators of adhesion events. Here we hypothesize a role for latrophilins in inter-neuronal contacts and the formation of neuronal networks and we review the most recent information on their role in neurons. We explore molecular, cellular and behavioral aspects related to latrophilin adhesion function in mice, zebrafish, Drosophila melanogaster and Caenorhabditis elegans, in physiological and pathophysiological conditions, including autism spectrum, bipolar, attention deficit and hyperactivity and substance use disorders.
Highlights
The adhesion G protein-coupled receptors latrophilins have been in the limelight for more than 20 years since their discovery as calcium-independent receptors for α-latrotoxin, a spider venom toxin with potent activity directed at neurotransmitter release from a variety of synapse types
Cellular and behavioral aspects related to latrophilin adhesion function in mice, zebrafish, Drosophila melanogaster and Caenorhabditis elegans, in physiological and pathophysiological conditions, including autism spectrum, bipolar, attention deficit and hyperactivity and substance use disorders
Fast-forward 22 years later what do we know about latrophilins? Here, after reviewing many studies, we can only start formulating the broad realm of their function: the widespread expression of latrophilin receptors in many tissues uncovers just the tip of the iceberg; their role in neuronal tissues places latrophilins at the crown of prototypical Adhesion G Protein-Coupled Receptors (aGPCR)
Summary
The teneurin-latrophilin pair has been the first fully functional complex to be characterized, as their interaction stabilizes intercellular adhesion and generates an intracellular signal involved in modulating calcium levels and/or cAMP related pathways (Muller et al, 2015; Li et al, 2018; Vysokov et al, 2018). It is still unclear how contact between both latrophilin and neurexin leads to neuronal synapse formation but their genetic interdependence in mice brains suggests a yet unknown functional mechanism that warrants further investigation (Tobaben et al, 2002).
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