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Actin-dependent alterations of dendritic spine morphology in shankopathies

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dc.contributor.author Sarowar, Tasnuva
dc.contributor.author Grabrucker, Andreas M.
dc.date.accessioned 2017-08-29T08:33:21Z
dc.date.available 2017-08-29T08:33:21Z
dc.date.issued 2016
dc.identifier.uri http://hdl.handle.net/10344/6034
dc.description peer-reviewed en_US
dc.description.abstract Shank proteins (Shank1, Shank2, and Shank3) act as scaffolding molecules in the postsynaptic density of many excitatory neurons. Mutations in SHANK genes, in particular SHANK2 and SHANK3, lead to autism spectrum disorders (ASD) in both human and mouse models. Shank3 proteins are made of several domains-the Shank/ProSAP N-terminal (SPN) domain, ankyrin repeats, SH3 domain, PDZ domain, a proline-rich region, and the sterile alpha motif (SAM) domain. Via various binding partners of these domains, Shank3 is able to bind and interact with a wide range of proteins including modulators of small GTPases such as RICH2, a RhoGAP protein, and βPIX, a RhoGEF protein for Rac1 and Cdc42, actin binding proteins and actin modulators. Dysregulation of all isoforms of Shank proteins, but especially Shank3, leads to alterations in spine morphogenesis, shape, and activity of the synapse via altering actin dynamics. Therefore, here, we highlight the role of Shank proteins as modulators of small GTPases and, ultimately, actin dynamics, as found in multiple in vitro and in vivo models. The failure to mediate this regulatory role might present a shared mechanism in the pathophysiology of autism-associated mutations, which leads to dysregulation of spine morphogenesis and synaptic signaling. en_US
dc.language.iso eng en_US
dc.publisher Hindawi Publishing Corporation en_US
dc.relation.ispartofseries Neural Plasticity;article ID: 8051861
dc.subject shank proteins en_US
dc.title Actin-dependent alterations of dendritic spine morphology in shankopathies en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2017-08-29T08:29:03Z
dc.description.version PUBLISHED
dc.identifier.doi 10.1155/2016/8051861
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2701160
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Neural plasticity
dc.description.status peer-reviewed


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