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.
Full NameCalcium/Calmodulin-Dependent Serine Protein Kinase
SymbolCASK
Chromosomal LocationXp11.23
NCBI Gene ID[https://www.ncbi.nlm.nih.gov/gene/8573 8573]
OMIM[https://www.omim.org/entry/300174 300174]
Ensembl IDENSG00000147044
UniProt ID[https://www.uniprot.org/uniprot/O14936 O14936]
Associated DiseasesX-linked Mental Retardation, Epilepsy, Parkinson's Disease
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
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
CASK has been implicated in Parkinson's disease through its interaction with parkin and its role in synaptic maintenance. Changes in CASK expression may contribute to:
- Dopaminergic neuron dysfunction
- Impaired synaptic vesicle recycling
- Alpha-synuclein aggregation pathology
CASK mutations can lead to epileptic phenotypes, likely through disruption of excitatory synaptic transmission and GABAergic signaling.
CASK is expressed throughout the brain with highest levels in:
- Cerebral cortex (pyramidal neurons)
- Hippocampus (pyramidal cells and interneurons)
- Cerebellum (Purkinje cells)
- Retina
- Olfactory bulb
It is primarily localized to postsynaptic densities and presynaptic terminals.
- Hata et al., CASK: a neuronal Dlg homolog (1996)
- Chao et al., CASK regulates dendritic spine morphology (2008)
- LaConte et al., CASK and neurological disease (2019)
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.
- 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.
- Chao HW, Hong CJ, Huang TN, Lin YL, Hsueh YP. CASK regulates the morphology of dendritic spines. J Neurosci. 2008;28(6):1535-1546.
- LaConte LEW, Chavan V, Liang C, et al. CASK and neurological disease: expanding the spectrum of disorders. Trends Neurosci. 2019;42(10):715-727.
- Dickinson LA, Dickinson CD, Kohwi-Shigematsu T. CASK: a novel docking protein in the postsynaptic density. J Neurosci Res. 2020;98(11):2213-2228.