Neurexins, latrophilins, and teneurins: Trans-synaptic signalling modules for synapse specification and organisation

Synapse specification and organisation rely on coordinated trans-synaptic interactions that couple molecular recognition to the assembly of pre- and postsynaptic compartments. While neurexins and cerebellin-mediated pathways have long been recognised as core determinants of synaptic identity, recent studies have identified latrophilins (LPHNs) as important organisers of defined excitatory pathways. In particular, the formation of teneurin-latrophilin-FLRT complexes has emerged as a key mechanism contributing to synaptic specificity in selected hippocampal and cortical circuits. Accumulating evidence further indicates that alternative splicing of LPHN3 configures intracellular signalling logic rather than merely modulating extracellular adhesion, thereby biasing the maturation of trans-synaptic contacts toward functional synapses. Here, we review recent advances that redefine latrophilin-dependent complexes as dynamic, signal-transducing synaptic modules linking molecular recognition to nanoscale synaptic organisation.