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

J Cell Sci. 2014 Dec 1;127(Pt 23):5038-51. doi: 10.1242/jcs.154542. Epub 2014 Oct 9.

Abstract

The acquisition of proper dendrite morphology is a crucial aspect of neuronal development towards 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 the 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 morphology. The mechanism operates during normal brain development, but its inhibition might have a protective influence on dendritic trees under toxic conditions, during which the silencing of CD44 expression prevents 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.

Keywords: CD44; Dendritic arborization; Extracellular matrix; Golgi fragmentation; Src kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology*
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / immunology
  • Dendrites / drug effects
  • Dendrites / enzymology*
  • Dendrites / immunology
  • Enzyme Activation
  • Female
  • Focal Adhesion Kinase 1 / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Glutamic Acid / toxicity*
  • Golgi Apparatus / enzymology*
  • Golgi Apparatus / immunology
  • HEK293 Cells
  • HeLa Cells
  • Hippocampus / drug effects
  • Hippocampus / enzymology*
  • Hippocampus / growth & development
  • Hippocampus / immunology
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology
  • Hyaluronan Receptors / metabolism*
  • Male
  • Morphogenesis
  • Mutation
  • Neurogenesis*
  • RNA Interference
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Transfection
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Hyaluronan Receptors
  • Glutamic Acid
  • Focal Adhesion Kinase 1
  • Ptk2 protein, rat
  • src-Family Kinases