Roles of Glypican and Heparan Sulfate at the Synapses

Abstract

Heparan sulfate proteoglycans (HSPGs) interact with various proteins through the HS chains and regulate many biological processes, and mutations in HSPG genes cause a variety of diseases. Recent studies in vertebrates and invertebrates have highlighted the importance of HSPGs glypicans in the development and function of synapses. Glypicans interact with various synapse-organizing proteins, such as LRRTMs and LAR family RPTPs, regulating synapse formation. Well-known presynaptic organizers, neurexins, function as HSPGs and bind to several proteins in common with glypicans through HS chains. Furthermore, glypicans regulate the postsynaptic levels of ionotropic glutamate receptors, controlling synaptic transmission. Mutations in glypican genes in model organisms affect synaptic development and function and cause abnormal behaviors. Recent human genetic studies also revealed associations of glypicans and HS with autism spectrum disorder. In this minireview, I describe the roles of glypicans and HS in synapse formation and neural plasticity as well as involvement in neurological diseases.