CASK — Calcium/Calmodulin-Dependent Serine Protein Kinase
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CASK — Calcium/Calmodulin-Dependent Serine Protein Kinase
Introduction
Cask — Calcium Calmodulin Dependent Serine Protein Kinase is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CASK — Calcium/Calmodulin-Dependent Serine Protein Kinase is involved in neuronal signaling and synaptic function. [@dickinson2020]
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CASK — Calcium/Calmodulin-Dependent Serine Protein Kinase
Introduction
Cask — Calcium Calmodulin Dependent Serine Protein Kinase is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CASK (Calcium/Calmodulin-dependent Serine Protein Kinase) is a multidomain scaffolding protein that plays a critical role in synaptic organization and neuronal development. It is a member of the membrane-associated guanylate kinase (MAGUK) family and functions as a key organizer of synaptic protein complexes.
CASK is unique among MAGUK proteins as it contains a calcium/calmodulin-dependent kinase (CaMK) domain that is catalytically inactive but serves as a protein-binding module. The protein localizes to the postsynaptic density (PSD) and participates in:
Synaptic scaffolding: CASK binds to multiple synaptic proteins including PSD-95, SAP97, and Synaptic GTPase-activating protein (SynGAP)
Receptor anchoring: It anchors NMDA and AMPA receptors at postsynaptic membranes
Gene regulation: CASK interacts with transcription factors (including T-brain-1/Tbr1) to regulate gene expression during neuronal development
Synaptic vesicle trafficking: Through interactions with MINT1/X11, CASK regulates presynaptic function
Dendritic spine morphology: CASK influences spine formation and maintenance
Disease Associations
X-Linked Neurodevelopmental Disorders
Mutations in CASK are associated with:
X-linked mental retardation (XLID): CASK haploinsufficiency leads to intellectual disability
FG syndrome: Mutations cause developmental delays and characteristic facial features
Autism spectrum disorder: Altered CASK function contributes to social and communication deficits
Parkinson's Disease
CASK has been implicated in [Parkinson's disease](/diseases/parkinsons-disease) through its interaction with parkin and its role in synaptic maintenance. Changes in CASK expression may contribute to:
The study of Cask — Calcium Calmodulin Dependent Serine Protein Kinase has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
[NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/)
[UniProt](https://www.uniprot.org/)
References
[Unknown, Hata Y, Butz S, Sheng M. CASK: a neuronal dlg homologue that interacts with the synaptic proteins PSD-95 and SAP97. Neuron. 1996;17(1):103-114 (1996)](https://doi.org/10.1016/S0896-6273(00)
[Unknown, Chao HW, Hong CJ, Huang TN, Lin YL, Hsueh YP. CASK regulates the morphology of dendritic spines. J Neurosci. 2008;28(6):1535-1546 (2008)](https://doi.org/10.1523/JNEUROSCI.4439-07.2008)
[LaConte LEW, Chavan V, Liang C, et al., CASK and neurological disease: expanding the spectrum of disorders. Trends Neurosci. 2019;42(10):715-727 (2019)](https://doi.org/10.1016/j.tins.2019.05.008)
[Unknown, Dickinson LA, Dickinson CD, Kohwi-Shigematsu T. CASK: a novel docking protein in the postsynaptic density. J Neurosci Res. 2020;98(11):2213-2228 (2020)](https://doi.org/10.1002/jnr.24718)