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Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood.

Levy AD, Omar MH, Koleske AJ - Front Neuroanat (2014)

Bottom Line: The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity.While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands.Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Neuroscience Program, Yale University New Haven, CT, USA ; Department of Molecular Biophysics and Biochemistry, Yale University New Haven, CT, USA.

ABSTRACT
Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer's disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

No MeSH data available.


Related in: MedlinePlus

Mechanisms of spine stabilization and remodeling by extracellular matrix (ECM) proteins. Extracellular matrix components can stabilize and remodel dendritic spines by a variety of different mechanisms. Structural restriction: ECM components such as chondroitin sulfate proteoglycans (CSPGs) can form a matrix around dendritic spines to provide extracellular rigidity and physically restrict spine motion. Adhesion: classical ECM proteins such as fibronectin and RGD-containing proteins can act as adhesion substrates and bind to integrin adhesion receptors to remodel spines. Ligand/receptor-driven intracellular signaling: ECM proteins like reelin function as ligands for non-adhesion receptors to drive intracellular signaling cascades that regulate spine remodeling and formation. Epitope unmasking by proteases: extracellular proteases such as tissue plasminogen activator (tPA) and the matrix metalloproteinase (MMPs) can cleave ECM proteins to reveal cryptic ligands that drive intracellular signaling to change spine morphology.
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Figure 2: Mechanisms of spine stabilization and remodeling by extracellular matrix (ECM) proteins. Extracellular matrix components can stabilize and remodel dendritic spines by a variety of different mechanisms. Structural restriction: ECM components such as chondroitin sulfate proteoglycans (CSPGs) can form a matrix around dendritic spines to provide extracellular rigidity and physically restrict spine motion. Adhesion: classical ECM proteins such as fibronectin and RGD-containing proteins can act as adhesion substrates and bind to integrin adhesion receptors to remodel spines. Ligand/receptor-driven intracellular signaling: ECM proteins like reelin function as ligands for non-adhesion receptors to drive intracellular signaling cascades that regulate spine remodeling and formation. Epitope unmasking by proteases: extracellular proteases such as tissue plasminogen activator (tPA) and the matrix metalloproteinase (MMPs) can cleave ECM proteins to reveal cryptic ligands that drive intracellular signaling to change spine morphology.

Mentions: Extracellular matrix molecules at synapses are likely candidates for regulators of synapse and dendritic spine stability. While studies have identified ECM receptors important for neuronal function and dendritic spine morphology, they often fail to identify the critical ECM ligands that drive these important processes. This failure may be partially due to the inherent difficulty of studying ECM components. Extracellular matrix molecules are secreted, so in the brain where many different cell types are intermingled, cell origin and site of function can be difficult to identify. The heterogenous cell population in the brain also complicates purification of ECM molecules from specific cell types. Additionally, many ECM molecules are large, such as laminins (800 kDa), and can have multiple interaction domains from the same molecule driving distinct pathways (Colognato and Yurchenco, 2000). Extracellular matrix biochemical activities are also altered by covalent modification and/or proteolytic processing, which can be triggered by synaptic activity (Nedivi et al., 1993; Qian et al., 1993; Sung et al., 1993; Szklarczyk et al., 2002; Chen et al., 2008; Horejs et al., 2014). Furthermore, it can be difficult to disentangle possible functions of ECM components in spine stabilization, e.g., providing extracellular rigidity, mediating spine-ECM adhesions, and/or inducing intracellular signaling cascades (Figure 2).


Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood.

Levy AD, Omar MH, Koleske AJ - Front Neuroanat (2014)

Mechanisms of spine stabilization and remodeling by extracellular matrix (ECM) proteins. Extracellular matrix components can stabilize and remodel dendritic spines by a variety of different mechanisms. Structural restriction: ECM components such as chondroitin sulfate proteoglycans (CSPGs) can form a matrix around dendritic spines to provide extracellular rigidity and physically restrict spine motion. Adhesion: classical ECM proteins such as fibronectin and RGD-containing proteins can act as adhesion substrates and bind to integrin adhesion receptors to remodel spines. Ligand/receptor-driven intracellular signaling: ECM proteins like reelin function as ligands for non-adhesion receptors to drive intracellular signaling cascades that regulate spine remodeling and formation. Epitope unmasking by proteases: extracellular proteases such as tissue plasminogen activator (tPA) and the matrix metalloproteinase (MMPs) can cleave ECM proteins to reveal cryptic ligands that drive intracellular signaling to change spine morphology.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202714&req=5

Figure 2: Mechanisms of spine stabilization and remodeling by extracellular matrix (ECM) proteins. Extracellular matrix components can stabilize and remodel dendritic spines by a variety of different mechanisms. Structural restriction: ECM components such as chondroitin sulfate proteoglycans (CSPGs) can form a matrix around dendritic spines to provide extracellular rigidity and physically restrict spine motion. Adhesion: classical ECM proteins such as fibronectin and RGD-containing proteins can act as adhesion substrates and bind to integrin adhesion receptors to remodel spines. Ligand/receptor-driven intracellular signaling: ECM proteins like reelin function as ligands for non-adhesion receptors to drive intracellular signaling cascades that regulate spine remodeling and formation. Epitope unmasking by proteases: extracellular proteases such as tissue plasminogen activator (tPA) and the matrix metalloproteinase (MMPs) can cleave ECM proteins to reveal cryptic ligands that drive intracellular signaling to change spine morphology.
Mentions: Extracellular matrix molecules at synapses are likely candidates for regulators of synapse and dendritic spine stability. While studies have identified ECM receptors important for neuronal function and dendritic spine morphology, they often fail to identify the critical ECM ligands that drive these important processes. This failure may be partially due to the inherent difficulty of studying ECM components. Extracellular matrix molecules are secreted, so in the brain where many different cell types are intermingled, cell origin and site of function can be difficult to identify. The heterogenous cell population in the brain also complicates purification of ECM molecules from specific cell types. Additionally, many ECM molecules are large, such as laminins (800 kDa), and can have multiple interaction domains from the same molecule driving distinct pathways (Colognato and Yurchenco, 2000). Extracellular matrix biochemical activities are also altered by covalent modification and/or proteolytic processing, which can be triggered by synaptic activity (Nedivi et al., 1993; Qian et al., 1993; Sung et al., 1993; Szklarczyk et al., 2002; Chen et al., 2008; Horejs et al., 2014). Furthermore, it can be difficult to disentangle possible functions of ECM components in spine stabilization, e.g., providing extracellular rigidity, mediating spine-ECM adhesions, and/or inducing intracellular signaling cascades (Figure 2).

Bottom Line: The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity.While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands.Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Neuroscience Program, Yale University New Haven, CT, USA ; Department of Molecular Biophysics and Biochemistry, Yale University New Haven, CT, USA.

ABSTRACT
Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer's disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

No MeSH data available.


Related in: MedlinePlus