Structural plasticity with preserved topology in the postsynaptic protein network

Blanpied, Thomas A.; Kerr, Justin M.; Ehlers, Michael

doi:10.1073/pnas.0711669105

Cited by 119 publications

(114 citation statements)

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“…To this end, the authors performed extended (1 h) time-lapse imaging of synaptic clusters composed of surface AMPARs. As expected from previous studies showing a substantial PSD flexibility (Blanpied et al, 2008), they observed that individual AMPAR clusters exhibit substantial and continuous changes in their morphology. In contrast to the continuously dynamic structure of AMPAR clusters, SEP fluorescence intensity was extremely stable over time.…”

Section: Review Of Kerr and Blanpiedsupporting

confidence: 61%

Microscale AMPAR Reorganization and Dynamics of the Postsynaptic Density: Figure 1.

Jurado¹,

Knafo²

2012

J. Neurosci.

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Section: Review Of Kerr and Blanpiedsupporting

confidence: 61%

Microscale AMPAR Reorganization and Dynamics of the Postsynaptic Density: Figure 1.

Jurado¹,

Knafo²

2012

J. Neurosci.

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“…The dynamic behavior of PSDs in living neurons in culture and in vivo has been typically visualized by GFP-tagged PSD-95, which localizes specifically in the PSD. This approach revealed that overall PSD structure undergoes continuous remodeling over a timescale of minutes to days (Blanpied et al 2008;Minerbi et al 2009). Within the PSD, however, mixing of existing PSD-95 molecules is relatively limited, suggesting that individual PSD-95 molecules, once integrated, maintain stable positions within the PSD (Blanpied et al 2008).…”

Section: Basal and Activity-dependent Protein Turnover In The Psdmentioning

confidence: 99%

The Postsynaptic Organization of Synapses

Sheng¹,

Kim²

2011

Cold Spring Harbor Perspectives in Biology

489

426

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The postsynaptic side of the synapse is specialized to receive the neurotransmitter signal released from the presynaptic terminal and transduce it into electrical and biochemical changes in the postsynaptic cell. The cardinal functional components of the postsynaptic specialization of excitatory and inhibitory synapses are the ionotropic receptors (ligandgated channels) for glutamate and g-aminobutyric acid (GABA), respectively. These receptor channels are concentrated at the postsynaptic membrane and embedded in a dense and rich protein network comprised of anchoring and scaffolding molecules, signaling enzymes, cytoskeletal components, as well as other membrane proteins. Excitatory and inhibitory postsynaptic specializations are quite different in molecular organization. The postsynaptic density of excitatory synapses is especially complex and dynamic in composition and regulation; it contains hundreds of different proteins, many of which are required for cognitive function and implicated in psychiatric illness. E xcitatory synapses on principal neurons of mammalian brain occur mainly on tiny protrusions called dendritic spines (Bourne and Harris 2008). In contrast, inhibitory synapses are formed on the shaft of dendrites, or on cell bodies and axon initial segments. The postsynaptic side of excitatory synapses differs from inhibitory synapses not only in their content of neurotransmitter receptors but also in their morphology and molecular composition and organization. In part because of their greater abundance and distinctive structure, much more is known about the postsynaptic organization of central excitatory (glutamatergic) synapses. THE POSTSYNAPTIC DENSITY OF EXCITATORY SYNAPSESExcitatory synapses are characterized by a morphological and functional specialization of the postsynaptic membrane called the postsynaptic density (PSD), which is usually located at the tip of the dendritic spine. The PSD contains the glutamate receptors that are activated by the glutamate neurotransmitter released from the presynaptic terminal, as well as a host of associated signaling and structural molecules. A set of abundant scaffold proteins holds together the PSD by binding to the glutamate receptors, other postsynaptic receptors and adhesion

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“…The PSD itself undergoes rapid morphology fluctuations in response to synaptic activity, and also widens concomitantly with expansion of the spine head during its maturation (Blanpied et al, 2008).…”

Section: Myosin II In Actin Organization During Dendritic Spine Maturmentioning

confidence: 99%

“…While many molecules that reside in the PSD have been identified, much less is known about the mechanisms that determine its morphology and organization (Peng et al, 2004;Cheng et al, 2006). The PSD is now thought to be dynamic and undergo rapid fluctuations in morphology (Blanpied et al, 2008;Frost et al, 2010b). Several proteins within the PSD scaffold reportedly interact with the actin cytoskeleton (Böckers et al, 2001;Sheng and Hoogenraad, 2007), raising the possibility that actin organization may underlie PSD morphology.…”

Section: Introductionmentioning

confidence: 99%

“…The post-synaptic density also undergoes rapid fluctuations in morphology driven by the actin cytoskeleton in response to synaptic activity (Marrs et al, 2001;Blanpied et al, 2008). Actin and actin-associated molecules such as cortactin, Arp2/3 complex, α-actinin, and others make up 12% of the PSD fraction, as estimated by mass spectrometry (Sheng and Hoogenraad, 2007).…”

mentioning

confidence: 99%

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Non-muscle Myosin-IIB and A-actinin-2 Determine Dendritic Spine Morphology and Post-synaptic Organization

Hodges¹

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II AbstractModulation of the actin cytoskeleton dictates the morphological changes associated with dendritic spine dynamics, which serve as the structural basis underlying learning and memory. These micron-sized protrusions mature from a filopodia-like morphology into a mushroom-shape with an enlarged post-synaptic density (PSD). The PSD contains an assembly of synaptic adhesion molecules, glutamate receptors, and signaling scaffolds; many of which respond to glutamate receptor activation and relay signals to the underlying cytoskeleton to induce structural changes in spine and PSD morphology.Non-muscle myosin IIB (MIIB) and α-actinin-2 (ACTN2) directly effect actin organization and both proteins localize to dendritic spines. Both molecules cross-link actin filaments and MIIB also mediates contraction through its ATPase activity.Knockdown of either ACTN2 or MIIB creates an immature spine morphology that fails to mature into a mushroom-shaped spine during development and in response to chemical stimulation. Additionally, loss of ACTN2 increases spine density. Expression of an actin cross-linking, non-contractile mutant, MIIB R709C, showed that spine maturation requires contractile activity. Additionally, di-phosphorylation of the myosin regulatory light chain (RLC) by Rho kinase is required for spine maturation. Inhibition of MIIB activity via blebbistatin treatment, knockdown, or expression of a mono-phosphomimetic mutant of RLC similarly abrogated spine maturation.MIIB and ACTN2 also determine PSD size, morphology, and placement in the spine. Loss of ACTN2 prevents the recruitment and stabilization of a PSD and NMDA-III type glutamate receptors in the spine, resulting in defective synaptic formation.Conversely, a PSD is still seen in neurons with MIIB knocked down, but its loss creates an elongated PSD morphology that is no longer restricted to the spine tip, resulting in a less-clustered distribution of NMDA receptors. In contrast, increased MIIB activity, through either over-expression of wild type MIIB or a RLC di-phosphomimetic mutant, enlarges the PSD area and creates an increased density of mature spines. These observations support a model whereby ACTN2 nucleates PSD formation and recruits the NMDA-type glutamate receptor to the spine, which leads to a functioning synapse.Subsequent NMDA receptor activation increases RLC di-phosphorylation to stimulate MIIB contractility, resulting in a mushroom-shaped spine with an enlarged PSD. IV AcknowledgementsI would like to thank my mentor, Rick Horwitz, for providing a great educational experience throughout my PhD candidacy. He is always available for discussion, albeit regarding my writing, experimental ideas, trouble-shooting, or personal issues. It is through Rick's invaluable coaching that I have learned how to be a successful scientist.

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Structural plasticity with preserved topology in the postsynaptic protein network

Cited by 119 publications

References 53 publications

Microscale AMPAR Reorganization and Dynamics of the Postsynaptic Density: Figure 1.

Microscale AMPAR Reorganization and Dynamics of the Postsynaptic Density: Figure 1.

The Postsynaptic Organization of Synapses

Non-muscle Myosin-IIB and A-actinin-2 Determine Dendritic Spine Morphology and Post-synaptic Organization

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