Regulation of Dendritic Spine Morphogenesis by Insulin Receptor Substrate 53, a Downstream Effector of Rac1 and Cdc42 Small GTPases

Choi, June-Seok; Ko, Jaewon; Rácz, Bence; Burette, A; Lee, Jae Ran; Kim, Se‐Ho; Na, Moonseok; Lee, Hyun Woo; Kim, Karam; Weinberg, Richard J.; Kim, Eunjoon

doi:10.1523/jneurosci.3212-04.2005

Cited by 204 publications

(192 citation statements)

References 64 publications

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“…Overexpression of IRSp53 in cultured neurons increases the density of dendritic spines without affecting spine length or width. Conversely, short-interfering RNAmediated knockdown of IRSp53 reduces spine density, length, and width 200 . In agreement with this, and indications from other in vitro studies [199][200][201]211 , IRSp53 −/− mice have fewer dendritic…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Accumulating evidence indicates that IRSp53 is an abundant component of multi-protein complexes on the postsynaptic side of excitatory synapses 199 and directly binds to PSD-95 and Shank/ProSAP [200][201][202] ( Figure 5). IRSp53 has been suggested to form a platform-like structure that organizes synaptic signaling to regulate dendritic spines through its ability to interact with F-actin and actin regulatory proteins 155,200,203,204 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Other scaffolds of the PSD include IRSp53 (insulin substrate protein of 53 kDa), which directly interacts with PSD-95 and Shank, and acts as a downstream effector of Rac1 for the regulation of actin polymerization in dendritic spines (Soltau et al 2004;Choi et al 2005). AKAP79/150 interacts with PSD-95 and functions as an adaptor bringing AKAP-associated enzymes such as protein kinase A and calcineurin to the PSD for regulation of glutamate receptors and synaptic function (Tavalin et al 2002;Bhattacharyya et al 2009).…”

Section: Other Psd Scaffoldsmentioning

confidence: 99%

The Postsynaptic Organization of Synapses

Sheng¹,

Kim²

2011

Cold Spring Harbor Perspectives in Biology

474

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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“…Accordingly, the espin 3 isoforms, which lack this proline-rich peptide, do not bind the IRSp53 SH3 domain [4]. Although implicated in actin cytoskeletal regulation in lamellipodia, ruffles, filopodia and dendritic spines [15,[74][75][76], evidence linking IRSp53 to stereocilia and microvilli is currently lacking. It is possible that the espin proline-rich peptides interact with other SH3 domain-containing scaffolding proteins in stereocilia and microvilli.…”

Section: Binding Pip2 and Ligands For Proline-rich Peptidesmentioning

confidence: 99%

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

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The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca 2+ . In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. KeywordsEspin; actin; hair cell; stereocilia; microvilli; sensory; deafness; taste The stereocilia and microvilli of vertebrate sensory cells and their actinbundling proteinsMany classes of vertebrate sensory cells detect chemical or mechanical stimuli through microvilli or their derivatives, such as stereocilia. These relatively long-lived, fingerlike specializations of the plasma membrane are built around a common cytoskeletal element -the parallel actin bundle (PAB) [1]. PABs consist of tightly packed collections of actin filaments cross-linked by actin-bundling proteins. The filaments are aligned along their longitudinal axis and display a uniform polarity with respect to their preferred ends for actin monomer addition, which in microvilli and stereocilia is positioned at the distal tip. The PAB displays hallmarks of a supramolecular scaffold that determines the placement, dimensions, flexibility and signaling properties of microvilli and stereocilia. Although filopodia also contain a PAB at their core and are believed to sense the local environment, they are considerably more dynamic and differ significantly from microvilli and stereocilia in their molecular composition and biogenesis [2].

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Regulation of Dendritic Spine Morphogenesis by Insulin Receptor Substrate 53, a Downstream Effector of Rac1 and Cdc42 Small GTPases

Cited by 204 publications

References 64 publications

Dendritic spine actin cytoskeleton in autism spectrum disorder

Dendritic spine actin cytoskeleton in autism spectrum disorder

The Postsynaptic Organization of Synapses

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

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