Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies
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 doma...
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| Format: | Article |
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Wiley
2016-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/8051861 |
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| author | Tasnuva Sarowar Andreas M. Grabrucker |
| author_facet | Tasnuva Sarowar Andreas M. Grabrucker |
| author_sort | Tasnuva Sarowar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e025c20759c04bd690b59e7e5448c4f2 |
| institution | OA Journals |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-e025c20759c04bd690b59e7e5448c4f22025-08-20T02:21:07ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/80518618051861Actin-Dependent Alterations of Dendritic Spine Morphology in ShankopathiesTasnuva Sarowar0Andreas M. Grabrucker1WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, 89081 Ulm, GermanyWG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, 89081 Ulm, GermanyShank 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.http://dx.doi.org/10.1155/2016/8051861 |
| spellingShingle | Tasnuva Sarowar Andreas M. Grabrucker Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies Neural Plasticity |
| title | Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies |
| title_full | Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies |
| title_fullStr | Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies |
| title_full_unstemmed | Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies |
| title_short | Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies |
| title_sort | actin dependent alterations of dendritic spine morphology in shankopathies |
| url | http://dx.doi.org/10.1155/2016/8051861 |
| work_keys_str_mv | AT tasnuvasarowar actindependentalterationsofdendriticspinemorphologyinshankopathies AT andreasmgrabrucker actindependentalterationsofdendriticspinemorphologyinshankopathies |