CD44: a novel synaptic cell adhesion molecule regulating structural and functional plasticity of dendritic spines

Mol Biol Cell. 2016 Dec 15;27(25):4055-4066. doi: 10.1091/mbc.E16-06-0423. Epub 2016 Oct 19.


Synaptic cell adhesion molecules regulate signal transduction, synaptic function, and plasticity. However, their role in neuronal interactions with the extracellular matrix (ECM) is not well understood. Here we report that the CD44, a transmembrane receptor for hyaluronan, modulates synaptic plasticity. High-resolution ultrastructural analysis showed that CD44 was localized at mature synapses in the adult brain. The reduced expression of CD44 affected the synaptic excitatory transmission of primary hippocampal neurons, simultaneously modifying dendritic spine shape. The frequency of miniature excitatory postsynaptic currents decreased, accompanied by dendritic spine elongation and thinning. These structural and functional alterations went along with a decrease in the number of presynaptic Bassoon puncta, together with a reduction of PSD-95 levels at dendritic spines, suggesting a reduced number of functional synapses. Lack of CD44 also abrogated spine head enlargement upon neuronal stimulation. Moreover, our results indicate that CD44 contributes to proper dendritic spine shape and function by modulating the activity of actin cytoskeleton regulators, that is, Rho GTPases (RhoA, Rac1, and Cdc42). Thus CD44 appears to be a novel molecular player regulating functional and structural plasticity of dendritic spines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / physiology
  • Dendritic Spines / metabolism
  • Dendritic Spines / physiology*
  • Hippocampus / cytology
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Hyaluronan Receptors / physiology*
  • Hyaluronic Acid / metabolism
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Rats
  • Signal Transduction / physiology
  • Synapses / metabolism
  • Synaptic Transmission / physiology
  • rho GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein / metabolism


  • CD44 protein, human
  • Cell Adhesion Molecules
  • Hyaluronan Receptors
  • Hyaluronic Acid
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein