Abstract
Dystroglycan (DG) is a cell membrane protein that binds to the extracellular matrix in various mammalian tissues. The function of DG has been well defined in embryonic development as well as in the proper migration of differentiated neuroblasts in the central nervous system (CNS). Although DG is known to be a target for matrix metalloproteinase-9 (MMP-9), cleaved in response to enhanced synaptic activity, the role of DG in the structural remodeling of dendritic spines is still unknown. Here, we report for the first time that the deletion of DG in rat hippocampal cell cultures causes pronounced changes in the density and morphology of dendritic spines. Furthermore, we noted a decrease in laminin, one of the major extracellular partners of DG. We have also observed that the lack of DG evokes alterations in the morphological complexity of astrocytes accompanied by a decrease in the level of aquaporin 4 (AQP4), a protein located within astrocyte endfeet surrounding neuronal dendrites and synapses. Regardless of all of these changes, we did not observe any effect of DG silencing on either excitatory or inhibitory synaptic transmission. Likewise, the knockdown of DG had no effect on Psd-95 protein expression. Our results indicate that DG is involved in dendritic spine remodeling that is not functionally reflected. This may suggest the existence of unknown mechanisms that maintain proper synaptic signaling despite impaired structure of dendritic spines. Presumably, astrocytes are involved in these processes.
Highlights
Dystroglycan (DG) is a cell membrane protein that binds to the extracellular matrix in various mammalian tissues
Our results show that the loss of DG causes changes in the complexity of dendritic arbors as well as in the shape and density of neuronal dendritic spines together with alterations in astrocyte morphology
To determine whether the deletion of DG influences the complexity of dendritic arbors in mature neurons, on day 20 in vitro, we performed imaging of cells infected with either the lentivirus carrying shRNA targeting DG (SH) or an empty virus encoding green fluorescent protein (GFP), and transfected with a red fluorescent protein (RFP)encoding vector
Summary
Dystroglycan (DG) is a cell membrane protein that binds to the extracellular matrix in various mammalian tissues. Studies during the past few years have indicated that astrocytes are involved in the proper functioning of excitatory synapses[15] These cells are characterized by high morphological complexity with extended and branched processes that are closely associated with synapses both at the structural level by covering dendritic spines and presynaptic terminals, and at the functional level through the release of g liotransmitters[16,17,18,19]. Our results show that the loss of DG causes changes in the complexity of dendritic arbors as well as in the shape and density of neuronal dendritic spines together with alterations in astrocyte morphology These changes were accompanied by lower expression of laminin and AQP4, known ligands of DG. It seems appropriate to consider the contribution of neural-glial interactions in maintaining normal synaptic transmission
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