CD44 regulates dendrite morphogenesis through Src tyrosine kinase-dependent positioning of the Golgi apparatus

Abstract

The acquisition of proper dendrite morphology is a critical aspect of neuronal development toward the formation of a functional network. The role of the extracellular matrix and its cellular receptors in this process has remained enigmatic. We report that CD44 adhesion molecule, the main hyaluronan receptor, is localized in dendrites and plays a crucial inhibitory role in dendritic tree arborization in vitro and in vivo. This novel function is exerted by the activation of Src tyrosine kinase, leading to the alteration of Golgi apparatus morphology. The mechanism operates during normal development, but its inhibition may have a protective influence on dendritic trees under toxic conditions, in which the silencing of CD44 expression prevented dendritic shortening induced by glutamate exposure. Overall, our results indicate a novel role for CD44 as an essential regulator of dendritic arbor complexity in both health and disease.