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Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease.

Stefen H, Chaichim C, Power J, Fath T - Neural Plast. (2016)

Bottom Line: In this review, we are discussing key factors that regulate the structure and dynamics of the actin cytoskeleton, the major cytoskeletal building block that supports the postsynaptic compartment.Special attention is given to the complex interplay of actin-associated proteins that are found in the synaptic specialization.We then discuss our current understanding of how disruption of these cytoskeletal elements may contribute to the pathological events observed in the nervous system under disease conditions with a particular focus on Alzheimer's disease pathology.

View Article: PubMed Central - PubMed

Affiliation: Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.

ABSTRACT
Disruption of synaptic function at excitatory synapses is one of the earliest pathological changes seen in wide range of neurological diseases. The proper control of the segregation of neurotransmitter receptors at these synapses is directly correlated with the intact regulation of the postsynaptic cytoskeleton. In this review, we are discussing key factors that regulate the structure and dynamics of the actin cytoskeleton, the major cytoskeletal building block that supports the postsynaptic compartment. Special attention is given to the complex interplay of actin-associated proteins that are found in the synaptic specialization. We then discuss our current understanding of how disruption of these cytoskeletal elements may contribute to the pathological events observed in the nervous system under disease conditions with a particular focus on Alzheimer's disease pathology.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the cytoskeleton-dependent trafficking of neurotransmitter receptors. Depicted are the key structures of the synapse and associated cytoskeletal molecules. Numbers indicate the following steps: (1) Myosin V traffics vesicles with receptors from the soma to the distal dendritic sites via microtubules (MT) [116]. MT plus ends are indicated by green circles. (2) Once within spines, myosin V transports receptors to plasma membrane via actin filaments [117]. (3) Anchoring of receptors in the PSD relies on myosin II contractile force on actin cytoskeleton in combination with constant actin treadmilling/turnover [48]. Lateral diffusion of receptors to and from the PSD to presynaptic regions can occur. (4) Receptor internalization involves myosin VI activity. Myosin VI transports internalized receptors to endosomal organelles, facilitating recycling of receptors back to the membrane or to degradation pathways [95]. (5) Receptors can also travel between the PSD and peripheral sites [118, 119].
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fig1: Schematic representation of the cytoskeleton-dependent trafficking of neurotransmitter receptors. Depicted are the key structures of the synapse and associated cytoskeletal molecules. Numbers indicate the following steps: (1) Myosin V traffics vesicles with receptors from the soma to the distal dendritic sites via microtubules (MT) [116]. MT plus ends are indicated by green circles. (2) Once within spines, myosin V transports receptors to plasma membrane via actin filaments [117]. (3) Anchoring of receptors in the PSD relies on myosin II contractile force on actin cytoskeleton in combination with constant actin treadmilling/turnover [48]. Lateral diffusion of receptors to and from the PSD to presynaptic regions can occur. (4) Receptor internalization involves myosin VI activity. Myosin VI transports internalized receptors to endosomal organelles, facilitating recycling of receptors back to the membrane or to degradation pathways [95]. (5) Receptors can also travel between the PSD and peripheral sites [118, 119].

Mentions: Synaptic function directly correlates with the composition of neurotransmitter receptor integration at the postsynaptic membrane. The cellular and molecular mechanisms of ionotropic receptor trafficking have been extensively reviewed [113–115]; here we will focus on regulatory mechanisms by which the cytoskeleton controls the neurotransmitter receptor expression profile in excitatory synapses. See Figure 1 for a schematic summarising the mechanisms involved in glutamate receptor trafficking.


Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease.

Stefen H, Chaichim C, Power J, Fath T - Neural Plast. (2016)

Schematic representation of the cytoskeleton-dependent trafficking of neurotransmitter receptors. Depicted are the key structures of the synapse and associated cytoskeletal molecules. Numbers indicate the following steps: (1) Myosin V traffics vesicles with receptors from the soma to the distal dendritic sites via microtubules (MT) [116]. MT plus ends are indicated by green circles. (2) Once within spines, myosin V transports receptors to plasma membrane via actin filaments [117]. (3) Anchoring of receptors in the PSD relies on myosin II contractile force on actin cytoskeleton in combination with constant actin treadmilling/turnover [48]. Lateral diffusion of receptors to and from the PSD to presynaptic regions can occur. (4) Receptor internalization involves myosin VI activity. Myosin VI transports internalized receptors to endosomal organelles, facilitating recycling of receptors back to the membrane or to degradation pathways [95]. (5) Receptors can also travel between the PSD and peripheral sites [118, 119].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4835652&req=5

fig1: Schematic representation of the cytoskeleton-dependent trafficking of neurotransmitter receptors. Depicted are the key structures of the synapse and associated cytoskeletal molecules. Numbers indicate the following steps: (1) Myosin V traffics vesicles with receptors from the soma to the distal dendritic sites via microtubules (MT) [116]. MT plus ends are indicated by green circles. (2) Once within spines, myosin V transports receptors to plasma membrane via actin filaments [117]. (3) Anchoring of receptors in the PSD relies on myosin II contractile force on actin cytoskeleton in combination with constant actin treadmilling/turnover [48]. Lateral diffusion of receptors to and from the PSD to presynaptic regions can occur. (4) Receptor internalization involves myosin VI activity. Myosin VI transports internalized receptors to endosomal organelles, facilitating recycling of receptors back to the membrane or to degradation pathways [95]. (5) Receptors can also travel between the PSD and peripheral sites [118, 119].
Mentions: Synaptic function directly correlates with the composition of neurotransmitter receptor integration at the postsynaptic membrane. The cellular and molecular mechanisms of ionotropic receptor trafficking have been extensively reviewed [113–115]; here we will focus on regulatory mechanisms by which the cytoskeleton controls the neurotransmitter receptor expression profile in excitatory synapses. See Figure 1 for a schematic summarising the mechanisms involved in glutamate receptor trafficking.

Bottom Line: In this review, we are discussing key factors that regulate the structure and dynamics of the actin cytoskeleton, the major cytoskeletal building block that supports the postsynaptic compartment.Special attention is given to the complex interplay of actin-associated proteins that are found in the synaptic specialization.We then discuss our current understanding of how disruption of these cytoskeletal elements may contribute to the pathological events observed in the nervous system under disease conditions with a particular focus on Alzheimer's disease pathology.

View Article: PubMed Central - PubMed

Affiliation: Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.

ABSTRACT
Disruption of synaptic function at excitatory synapses is one of the earliest pathological changes seen in wide range of neurological diseases. The proper control of the segregation of neurotransmitter receptors at these synapses is directly correlated with the intact regulation of the postsynaptic cytoskeleton. In this review, we are discussing key factors that regulate the structure and dynamics of the actin cytoskeleton, the major cytoskeletal building block that supports the postsynaptic compartment. Special attention is given to the complex interplay of actin-associated proteins that are found in the synaptic specialization. We then discuss our current understanding of how disruption of these cytoskeletal elements may contribute to the pathological events observed in the nervous system under disease conditions with a particular focus on Alzheimer's disease pathology.

No MeSH data available.


Related in: MedlinePlus