Linking the Teneurin-Latrophilin Interaction with Glucose Metabolism: Role of the Teneurin C-terminal Associated Peptide (TCAP)-1

A newly discovered neuropeptide called teneurin C-terminal associated peptide (TCAP) exists in four isoforms, and is functionally related to its proprotein 'teneurin'. TCAP-1 is expressed as a separate mRNA distinct from teneurin-1 and its mature peptide binds to the latrophilin (LPHN) G-protein coupled receptors (GPCRs) and associates with beta-dystroglycan, to activate a neurotrophic-like signal cascade, stimulating energy production and regulating cytoskeletal development. I found reduced levels of diacylglycerol (DAG), but not inositol triphosphate (IP3), in TCAP-1-treated hippocampal cells, indicating that TCAP-1 may downregulate the LPHN pathway. Immunocytochemical analyses show TCAP-1 co-localizes with LPHN-1 in hippocampal cells. I also confirm the endogenous mRNA expression of LPHN-1 and -3, and all four teneurins and TCAPs in mouse hippocampal and hypothalamic cells. An in vivo approach established that TCAP-1 significantly reduces serum glucose levels in diabetic rodents. Thus, the teneurin/TCAP-1-LPHN interaction may strengthen synapse formation and increase brain glucose utilization during stressful conditions.