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

Matylda Roszkowska, Anna Skupien, Tomasz Wójtowicz, Anna Konopka, Adam Gorlewicz, Magdalena Kisiel, Marek Bekisz, Blazej Ruszczycki, Hubert Dolezyczek, Emilia Rejmak, Ewelina Knapska, Jerzy W. Mozrzymas, Jakub Wlodarczyk, Grzegorz M. Wilczynski, Joanna Dzwonek

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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.

Original languageEnglish
Pages (from-to)4055-4066
Number of pages12
JournalMolecular Biology of the Cell
Issue number25
Early online date19 Oct 2016
Publication statusPublished - 15 Dec 2016
Externally publishedYes


  • Synaptic cell adhesion
  • CD44
  • transmembrane receptors
  • synaptic plasticity


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