Back to Search
Start Over
Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies
- Source :
- Neural Plasticity, Neural Plasticity, Vol 2016 (2016)
- Publication Year :
- 2016
-
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, andβPIX, 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 multiplein vitroandin vivomodels. 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.
- Subjects :
- 0301 basic medicine
Dendritic spine
Dendritic Spines
PDZ domain
Presynaptic Terminals
Nerve Tissue Proteins
Review Article
Biology
SH3 domain
lcsh:RC321-571
GTP Phosphohydrolases
03 medical and health sciences
Animals
Humans
Actin-binding protein
Autistic Disorder
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Actins
Cell biology
SHANK2
030104 developmental biology
Neurology
biology.protein
Ankyrin repeat
Neurology (clinical)
Postsynaptic density
Sterile alpha motif
Subjects
Details
- ISSN :
- 16875443
- Volume :
- 2016
- Database :
- OpenAIRE
- Journal :
- Neural plasticity
- Accession number :
- edsair.doi.dedup.....e9c4607ac8bf063fa9754c75298b2006