LAR, liprin alpha and the regulation of active zone morphogenesis

Abstract

Active zones are protein-rich regions of neurons that act as sites of synaptic vesicle fusion and neurotransmitter release at the pre-synaptic terminus. Although the discovery that the receptor protein tyrosine phosphatase LAR and its cytoplasmic binding partner liprin alpha are essential for proper active zone formation is nearly a decade old, the underlying mechanisms are still poorly understood. Recent studies have identified a number of binding partners for both LAR and liprin alpha, several of which play key roles in active zone assembly. These include nidogen, dallylike and syndecan--extracellular ligands for LAR that regulate synapse morphogenesis. In addition, liprin-alpha-interacting proteins such as ERC2, RIM and the MALS/Veli-Cask-Mint1 complex cooperate to form a dense molecular scaffold at the active zone that is crucial for proper synaptic function. These studies allow us to propose testable models of LAR and liprin alpha function, and provide insights into the fundamental molecular mechanisms of synapse formation and stabilization.