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Published on: December 10, 2015
Deletion of CASK in mice is lethal and impairs synaptic function
Deniz Atasoy1, Susanne Schoch, Angela Ho
1Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Summary
Calcium/calmodulin-dependent serine protein kinase (CASK) is essential for mouse survival. CASK deficiency alters synaptic release but not core neuronal functions, indicating a selective role in neuronal physiology.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- CASK (Calcium/calmodulin-dependent serine protein kinase) is a multidomain protein with suggested roles in synaptic scaffolding, ion channel organization, and gene transcription.
- Its precise physiological importance in vivo remains incompletely defined.
Purpose of the Study:
- To elucidate the essential functions of CASK by analyzing its physiological importance in vivo.
- To define the role of CASK in neuronal development and synaptic function.
Main Methods:
- Generation and analysis of CASK knockdown and knockout mouse models.
- Biochemical analysis of CASK-interacting proteins in CASK-deficient neurons.
- Electrophysiological and ultrastructural analysis of synapses in CASK-deficient neurons.
Main Results:
- CASK knockout mice exhibit perinatal lethality and a partially penetrant cleft palate syndrome.
- CASK deficiency leads to decreased levels of interacting proteins (Mints, Veli/Mals, neurexins) and increased neuroligin 1.
- Neurons lacking CASK show altered spontaneous neurotransmitter release (increased glutamatergic, decreased GABAergic) but normal evoked release and synapse structure.
Conclusions:
- CASK is indispensable for mouse survival, highlighting its critical physiological role.
- CASK is not required for fundamental neuronal activities like excitability or evoked neurotransmission.
- CASK plays a selective role in regulating spontaneous synaptic release, underscoring its specific importance in neuronal function.
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