SHANK2 plays an important role in neuronal polarity

Abstract

SHANK2 is an important scaffolding protein present in the postsynaptic density (PSD) of mature neurons. The PSD region is important for organizing the AMPA and NMDA receptors on the membrane, and for interaction with the cytoskeleton. It is known that SHANK2 plays a role in developmental neuronal diseases, such as autism spectrum disorder. At DIV7 and DIV14 of the development, SHANK2 was found to be present in the axonal growth cones. Here, we characterized the function of SHANK2 in the axonal growth cones. We also questioned whether SHANK2 is present at an earlier stage of the development. This study showed that SHANK2 is present at DIV4 of the development. We found SHANK2 localization in the axonal growth cones, but also in the dendritic growth cones. By performing knockdown experiments, we demonstrate that absence of SHANK2 results in mislocalization of the AIS proteins TRIM46 and AnkG to the dendrites in DIV4 hippocampal neurons. We also observed an altered microtubule organization by overexpressing SHANK2 in COS-7 cells. These results indicate that SHANK2 plays a role in neuronal polarity in early stages of the development, next to its scaffolding role in mature neurons.