Deletion of CASK in mice is lethal and impairs synaptic function.

Deletion of CASK in mice is lethal and impairs synaptic function. Research Abstract Details 

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Deletion of CASK in mice is lethal and impairs synaptic function. Abstract Text:

Deniz Atasoy,Susanne Schoch,Angela Ho,Krisztina A Nadasy,Xinran Liu,Weiqi Zhang,Konark Mukherjee,Elena D Nosyreva,Rafael Fernandez-Chacon,Markus Missler,Ege T Kavalali,Thomas C ,

CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca2+/calmodulin-kinase domain, central PDZ and SH3 domains, and a C-terminal guanylate kinase domain. Many potential activities for CASK have been suggested, including functions in scaffolding the synapse, in organizing ion channels, and in regulating neuronal gene transcription. To better define the physiological importance of CASK, we have now analyzed CASK "knockdown" mice in which CASK expression was suppressed by approximately 70%, and CASK knockout (KO) mice, in which CASK expression was abolished. CASK knockdown mice are viable but smaller than WT mice, whereas CASK KO mice die at first day after birth. CASK KO mice exhibit no major developmental abnormalities apart from a partially penetrant cleft palate syndrome. In CASK-deficient neurons, the levels of the CASK-interacting proteins Mints, Veli/Mals, and neurexins are decreased, whereas the level of neuroligin 1 (which binds to neurexins that in turn bind to CASK) is increased. Neurons lacking CASK display overall normal electrical properties and form ultrastructurally normal synapses. However, glutamatergic spontaneous synaptic release events are increased, and GABAergic synaptic release events are decreased in CASK-deficient neurons. In contrast to spontaneous neurotransmitter release, evoked release exhibited no major changes. Our data suggest that CASK, the only member of the membrane-associated guanylate kinase protein family that contains a Ca2+/calmodulin-dependent kinase domain, is required for mouse survival and performs a selectively essential function without being in itself required for core activities of neurons, such as membrane excitability, Ca2+-triggered presynaptic release, or postsynaptic receptor functions.

Deletion of CASK in mice is lethal and impairs synaptic function. Publishing Authors By Initials

D Atasoy,S Schoch,A Ho,KA Nadasy,X Liu,W Zhang,K Mukherjee,ED Nosyreva,R Fernandez-Chacon,M Missler,ET Kavalali,TC ,

For similar nervous system: synapses research abstracts see: nervous system: synapses research

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Deletion of CASK in mice is lethal and impairs synaptic function. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 2525-30

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 7

MONTH: 02

YEAR: 2007

Deletion of CASK in mice is lethal and impairs synaptic function. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Deletion of CASK in mice is lethal and impairs synaptic function. Keywords Mesh Terms:

KEYWORDS: Synapses

MESH TERMS: physiology

Chemical & Substance for Abstract: Deletion of CASK in mice is lethal and impairs synaptic function. Information

Substance Name: Guanylate Kinase

Registry Number: EC 2.7.4.8

Grant and Affiliation Information for Deletion of CASK in mice is lethal and impairs synaptic function.

AFFILIATION: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.

Country: United States

AGENCY: United States NIMH

GRANT: R37 MH52804-08

ACRONYM: MH

MEDLINETA: Proc Natl Acad Sci U S A

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