title: CD44: a novel synaptic cell adhesion molecule regulating structural and functional plasticity of dendritic spines.
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.
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.|Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Matylda
authors: M
authors: Roszkowska
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Anna
authors: A
authors: Skupien
authors: Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors: Tomasz
authors: T
authors: Wójtowicz
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Anna
authors: A
authors: Konopka
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Adam
authors: A
authors: Gorlewicz
authors: Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors: Magdalena
authors: M
authors: Kisiel
authors: Laboratory of Visual System, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Marek
authors: M
authors: Bekisz
authors: Laboratory of Imaging Tissue Structure and Function, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Blazej
authors: B
authors: Ruszczycki
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Hubert
authors: H
authors: Dolezyczek
authors: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Emilia
authors: E
authors: Rejmak
authors: Laboratory of Emotions Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Ewelina
authors: E
authors: Knapska
authors: Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors: Jerzy W
authors: JW
authors: Mozrzymas
authors: Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Jakub
authors: J
authors: Wlodarczyk
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors: Grzegorz M
authors: GM
authors: Wilczynski
authors: Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland j.dzwonek@nencki.gov.pl.
authors: Joanna
authors: J
authors: Dzwonek
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein