TY - JOUR
T1 - CD44
T2 - a novel synaptic cell adhesion molecule regulating structural and functional plasticity of dendritic spines
AU - Roszkowska, Matylda
AU - Skupien, Anna
AU - Wójtowicz, Tomasz
AU - Konopka, Anna
AU - Gorlewicz, Adam
AU - Kisiel, Magdalena
AU - Bekisz, Marek
AU - Ruszczycki, Blazej
AU - Dolezyczek, Hubert
AU - Rejmak, Emilia
AU - Knapska, Ewelina
AU - Mozrzymas, Jerzy W
AU - Wlodarczyk, Jakub
AU - Wilczynski, Grzegorz M
AU - Dzwonek, Joanna
N1 - © 2016 Roszkowska et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
PY - 2016/12/15
Y1 - 2016/12/15
N2 - 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.
AB - 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.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85006446632&partnerID=8YFLogxK
U2 - 10.1091/mbc.E16-06-0423
DO - 10.1091/mbc.E16-06-0423
M3 - Article
C2 - 27798233
SN - 1059-1524
VL - 27
SP - 4055
EP - 4066
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 25
ER -