The Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) are differentially expressed in the nervous system and were recently found to instruct presynaptic and mediate postsynaptic glutamatergic differentiation, with LRRTM1 and LRRTM2 most potent at inducing presynaptic differentiation. Each LRRTM protein is a type I transmembrane containing ten extracellular leucine-rich repeats and a short intracellular tail and has a developmentally regulated pattern distinct from all others. LRRTM2 interacts with PSD-95 and regulates the surface expression of AMPA receptors. LRRTM2 also functions as a neurexin ligand, binding both Neurexin 1-alpha and -beta, suggesting that LRRTM2-Neurexin1 interaction plays a critical role in regulatory excitatory synapse development.
