Synaptic Cell Adhesion: A Structural Perspective

Cell adhesion molecules (CAMs) play critical roles in mediating intercellular interactions in the context of the nervous system, such as guiding neuronal development, synapse formation and maturation, and synaptic plasticity. In addition to their extracellular adhesive roles, most CAMs induce intracellular signaling events and scaffold large protein complexes through intracellular domains. The molecular biology of how CAMs regulate synaptic development and function has been hugely advanced by decades of structural biology. These structures have illuminated multiple modes of CAM regulation, including how alternative splicing regulates CAM homotypic and heterotypic interactions. CAMs are diverse in size and contain a variety of adhesion domain classes such as immunoglobulin (Ig), leucine-rich repeats (LRR), and laminin G/neurexin/sex hormone (LNS). In this chapter, we detail structures of key synaptic adhesion complexes, including a mechanistic explanation of how these structures have informed functional work. Detailing the structural basis of synaptic adhesion provides a foundation for deciphering the complex interactions underlying neuronal connectivity and function in health and disease.