Camguk, Lin-2, and CASK: novel membrane-associated guanylate kinase homologs that also contain CaM kinase domains

Dimitratos, Spiros D.; Woods, Daniel F.; Bryant, Peter J.

doi:10.1016/s0925-4773(97)00668-0

Cited by 52 publications

(42 citation statements)

References 9 publications

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“…Membrane-associated guanylate kinase proteins (MAGUKs) form the most prominent family of scaffolding molecules associated with intercellular junctions. MAGUKs are characterized by three canonical domains: N-terminal PDZ domains, a central SH3 domain, and a C-terminal guanylate kinase domain (1,2). A large number of MAGUKs with these domains were described, but CASK is the only MAGUK that contains an additional large N-terminal domain with homology to calcium/ calmodulin-dependent protein kinase II␣ (3).…”

mentioning

confidence: 99%

Deletion of CASK in mice is lethal and impairs synaptic function

Atasoy

Schoch

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

195

219

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CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca 2؉ /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 Ϸ70%, 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 Ca 2؉ /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, Ca 2؉ -triggered presynaptic release, or postsynaptic receptor functions.CaM kinase ͉ MAGUK ͉ neurexin ͉ neurotransmitter release ͉ synapse

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mentioning

confidence: 99%

Deletion of CASK in mice is lethal and impairs synaptic function

Atasoy

Schoch

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

195

219

View full text Add to dashboard Cite

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“…CASK was originally identified as a neurexin-interacting partner in rat brain [2]. CASK is a membrane-associated guanylate kinase protein (MAGUK) [3] and regulates lineage-specific decisions in a variety of taxa, including nematodes and mammals [4,5]. CASK is considered to be a pseudokinase because the functionally important residues within CaMKII domain are mutated [6].…”

Section: Introductionmentioning

confidence: 99%

Acheron, an novel LA antigen family member, binds to cask and forms a complex with id transcription factors

Weng¹,

Kim

Valavanis³

et al. 2009

Cellular and Molecular Biology Letters

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Acheron, a Lupus antigen ortholog, was identified as a novel death-associated transcript from the intersegmental muscles of the mothManduca sexta. Acheron is phylogenetically-conserved and represents a new sub-family of Lupus antigen proteins. Acheron is expressed predominantly in neurons and muscle in vertebrates, and regulates several developmental events including myogenesis, neurogenesis and possibly metastasis. Using Acheron as bait, we performed a yeast two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel CASK/Lin-2 isoform, as an Acheron binding partner. Acheron and CASK-C bind via the C-terminus of Acheron and the CaMKII-like domain of CASK-C. Co-immunoprecipitation assays verify this interaction and demonstrate that Acheron also forms a complex with all members of the Id (inhibitor of differentiation) proteins. Taken together, these data suggest a mechanism by which Acheron may regulate development and pathology.

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“…Sera were screened against the antigens in ELISAs and in Western blots of purified N-or C-terminal EAG fragments as appropriate. Purified GST-CMG 152-897 was used for the immunization of guinea pigs as described previously (Dimitratos et al, 1997). Phosphospecific anti-EAG antibody was a gift from Leslie Griffith (Brandeis University, Waltham, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Recent work has demonstrated that Drosophila CaMKII interacts with the Camguk (CMG) adaptor protein (Lu et al, 2003). CMG is a member of the membrane-associated guanylate kinase (MAGUK) family of adaptor proteins and the Drosophila ortholog of CASK and Lin-2 (Hata et al, 1996;Hoskins et al, 1996;Dimitratos et al, 1997;Butz et al, 1998). CMG/CASK/ LIN-2 is unique in that the N terminal (NT) displays considerable homology to CaMKII.…”

Section: Introductionmentioning

confidence: 99%

Camguk/CASK Enhances Ether-Á-Go-Go Potassium Current by a Phosphorylation-Dependent Mechanism

Marble¹,

Hegle²,

Snyder³

et al. 2005

J. Neurosci.

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Signaling complexes are essential for the modulation of excitability within restricted neuronal compartments. Adaptor proteins are the scaffold around which signaling complexes are organized. Here, we demonstrate that the Camguk (CMG)/CASK adaptor protein functionally modulates Drosophila Ether-á-go-go (EAG) potassium channels. Coexpression of CMG with EAG in Xenopus oocytes results in a more than twofold average increase in EAG whole-cell conductance. This effect depends on EAG-T787, the residue phosphorylated by calcium-and calmodulin-dependent protein kinase II (Wang et al., 2002). CMG coimmunoprecipitates with wild-type and EAG-T787A channels, indicating that T787, although necessary for the effect of CMG on EAG current, is not required for the formation of the EAG-CMG complex. Both CMG and phosphorylation of T787 increase the surface expression of EAG channels, and in COS-7 cells, EAG recruits CMG to the plasma membrane. The interaction of EAG with CMG requires a noncanonical Src homology 3-binding site beginning at position R1037 of the EAG sequence. Mutation of basic residues, but not neighboring prolines, prevents binding and prevents the increase in EAG conductance. Our findings demonstrate that membrane-associated guanylate kinase adaptor proteins can modulate ion channel function; in the case of CMG, this occurs via an increase in the surface expression and phosphorylation of the EAG channel.

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Camguk, Lin-2, and CASK: novel membrane-associated guanylate kinase homologs that also contain CaM kinase domains

Cited by 52 publications

References 9 publications

Deletion of CASK in mice is lethal and impairs synaptic function

Deletion of CASK in mice is lethal and impairs synaptic function

Acheron, an novel LA antigen family member, binds to cask and forms a complex with id transcription factors

Camguk/CASK Enhances Ether-Á-Go-Go Potassium Current by a Phosphorylation-Dependent Mechanism

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