The adaptor protein SKT interacts with PSD-95 and SHANK3 and affects synaptic functions
Alessandro Morellato1, Mario De Gregorio1, Costanza Angelini1
1Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Cell Reports
|September 2, 2025
Summary
The SKT protein adaptor is crucial for synaptic function, impacting dendritic spine structure and neuronal development. Its absence in knockout mice leads to neurological and cognitive deficits, highlighting its role in brain health.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The postsynaptic density (PSD) is a critical protein complex regulating synaptic function.
- Disruptions in PSD composition are linked to neurological disorders like autism and cognitive impairment.
Purpose of the Study:
- To investigate the role of the SKT adaptor protein in the postsynaptic density.
- To elucidate SKT's contribution to synaptic structure, function, and associated neurological processes.
Main Methods:
- Utilized SKT-knockout (KO) mouse models.
- Analyzed dendritic spine density and morphology.
- Assessed RhoA and Rac1 GTPase activity.
- Examined neuronal synchronization and maturation in vitro.
- Conducted behavioral tests for motor, cognitive, and executive functions.
Main Results:
- SKT adaptor protein is integral to the synaptic network, binding PSD-95 and SHANK3.
- SKT-KO mice exhibit abnormal dendritic spine density and morphology with dysregulated RhoA/Rac1 activity.
- KO-derived neurons show delayed synchronization and maturation, with impaired glutamatergic signaling.
- SKT-KO mice display behavioral deficits including increased self-grooming, impaired motor coordination, and altered cognitive functions.
Conclusions:
- SKT is essential for the structural and functional organization of the postsynaptic density.
- SKT regulates synaptic function through interactions with key PSD components.
- SKT plays a vital role in normal neuronal development and cognitive processes.
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