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Mol Biol Cell. 2016 Dec 15;27(25):4055-4066. Epub 2016 Oct 19.

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

Author information

1
Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
2
Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
3
Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, 50-368 Wroclaw, Poland.
4
Laboratory of Visual System, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
5
Laboratory of Imaging Tissue Structure and Function, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
6
Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
7
Laboratory of Emotions Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
8
Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland j.dzwonek@nencki.gov.pl.

Abstract

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.

PMID:
27798233
PMCID:
PMC5156546
[Available on 2017-03-02]
DOI:
10.1091/mbc.E16-06-0423
[Indexed for MEDLINE]
Free PMC Article

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