LAR, liprin α 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 α 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 α, 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-α-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 α function, and provide insights into the fundamental molecular mechanisms of synapse formation and stabilization.