Slob, a Novel Protein that Interacts with the Slowpoke Calcium-Dependent Potassium Channel

Schopperle, William M.; Holmqvist, Mats; Zhou, Yi; Wang, Jing; Wang, Zheng; Griffith, Leslie C.; Keselman, Inna; Kusinitz, Felicity; Dagan, Daniel; Levitan, Irwin B.

doi:10.1016/s0896-6273(00)80995-2

Cited by 109 publications

(94 citation statements)

References 51 publications

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“…In these assays we stimulated PKA activity intimately associated with the channel by applying cAMP to the intracellular face of isolated inside-out patches. As previously reported (17) the effects of cAMP in this system are dependent upon the presence of Mg-ATP, and the actions of cAMP are completely abolished by the PKA inhibitor peptide PKI [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] . Although STREX channels are inhibited whereas ZERO channels are activated by PKA closely associated with the channel (17), the short LZ1-competing peptides effectively blocked PKAdependent regulation of either splice variant.…”

Section: Pkac Docking With Mouse Bk Channel Variants Mediated Via a Lz1supporting

confidence: 80%

“…A single gene (KCNMA1) encodes for the pore-forming ␣-subunits of BK channels in all mammalian tissues (9). Phenotypic variation in native BK channels results from extensive alternative exon splicing of the ␣-subunit (6, 9, 10) as well as through interaction with regulatory ␤-subunits and accessory proteins (11)(12)(13). The BK channel ␣-subunit is a target for regulation by multiple protein kinases and protein phosphatases (3, 14 -18), and several protein kinases have been reported to co-immunoprecipitate with mammalian BK channels (3,16,17).…”

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confidence: 99%

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Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

Tian

Coghill

MacDonald

et al. 2003

Journal of Biological Chemistry

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Large conductance, calcium-and voltage-activated potassium (BK) channels control excitability in many tissues and are regulated by several protein kinases and phosphatases that remain associated with the channels in cell-free patches of membrane. Here, we report the identification of a highly conserved, non-canonical, leucine zipper (LZ1) in the C terminus of mammalian BK channels that is required for cAMP-dependent protein kinase ( Reversible protein phosphorylation represents a fundamental cellular regulatory mechanism to control the activity and function of plasma membrane ion channels (1). The co-ordination, specificity, and compartmentalization of ion channel regulation by reversible protein phosphorylation is facilitated by assembly with signaling complexes comprising cognate protein kinases and protein phosphatases. Assembly of ion channels with signaling complexes typically results from multiple protein-protein interactions mediated by distinct interaction domains (2) allowing signaling molecules to interact directly with an ion channel or indirectly as part of a higher order complex.Large conductance calcium-and voltage-activated potassium (BK) channels have been widely exploited as models of ion channel regulation by reversible protein phosphorylation; however, the molecular basis for kinase and phosphatase assembly with the BK channel is largely unknown

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Section: Pkac Docking With Mouse Bk Channel Variants Mediated Via a Lz1supporting

confidence: 80%

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confidence: 99%

Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

Tian

Coghill

MacDonald

et al. 2003

Journal of Biological Chemistry

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“…Yeast Two-hybrid Screen-The yeast two-hybrid screen was performed according to a protocol described previously (31). In brief, a Drosophila calcium/calmodulin-dependent kinase II (CaMKII) R5 isoform (32) variable region plus association domain cDNA was inserted into pEG202 and used as a bait to screen a Drosophila adult head cDNA library (provided by J. Huang and M. Rosbash, Brandeis University, Waltham, MA) in vector pJG4-5.…”

Section: Methodsmentioning

confidence: 99%

“…The pcDNA3-HA mammalian expression vector was derived from pcDNA3 (Invitrogen) by introducing a short fragment encoding the HA epitope tag into the polylinker region (31). To obtain a pGEX vector allowing expression of a GST fusion protein which could be labeled by protein kinase, the polylinker region of pGSTag (provided by M. Neville and M. Rosbash, Brandeis University, Waltham, MA) was modified to allow in-frame fusions.…”

Section: Methodsmentioning

confidence: 99%

Identification and Characterization of a SUMO-1 Conjugation System That Modifies Neuronal Calcium/Calmodulin-dependent Protein Kinase II in Drosophila melanogaster

Long

Griffith

2000

Journal of Biological Chemistry

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Drosophila Uba2 and Ubc9 SUMO-1 conjugation enzyme homologs (DmUba2 and DmUbc9) were isolated as calcium/calmodulin-dependent kinase II (CaMKII) interacting proteins by yeast two-hybrid screening of an adult head cDNA library. We found that at least one isoform of Drosophila neuronal CaMKII is conjugated to DmSUMO-1 in vivo. The interactions observed in the two-hybrid screen may therefore reflect catalytic events. To understand the role of SUMO conjugation in the brain, we undertook a characterization of the system. The other required components of the system, Drosophila Aos1 and SUMO-1 (DmAos1 and DmSUMO-1), were identified in expressed sequence tag data base searches. Purified recombinant DmUba2/DmAos1 dimer can activate DmSUMO-1 in vitro and transfer Dm-SUMO-1 to recombinant DmUbc9. DmSUMO-1 conjugation occurs in all developmental stages of Drosophila and in the adult central nervous system. Overexpression of a putative dominant negative DmUba2(C175S) mutant protein in the Drosophila central nervous system resulted in an increase in overall DmSUMO-1 conjugates and a base-sensitive p120 species, which is likely to be DmUba2(C175S) linked to endogenous DmSUMO-1 through an oxygen ester bond. Overexpression of DmUba2(wt) protein in vivo also led to increased levels of DmSUMO-1 conjugates. High level overexpression of either DmUba2(wt) or DmUba2(C175S) in the Drosophila central nervous system caused pupal and earlier stage lethality. Expression in the developing eye led to a rough eye phenotype with retinal degeneration. These results suggest that normal SUMO conjugation is essential in the differentiated nervous system and reveal a potential novel mechanism that regulates neuronal calcium/calmodulin-dependent protein kinase II function.

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“…The Ca V channels at the presynaptic active zone form a protein complex with several anchoring proteins (24)(25)(26), such as Mint-1, CASK, and Rab3-interacting molecule (RIM) binding proteins (RBP). In Drosophila, two cytosolic regulatory proteins, Slob and dSLIP, and two protein kinases, Src and PKAc, are able to assemble with the slo ␣-subunit (27)(28)(29). In vertebrates, however, only kinases, such as Src and Syk, have been reported to interact with this subunit (30)(31)(32).…”

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confidence: 99%

Association of β-catenin with the α-subunit of neuronal large-conductance Ca ²⁺ -activated K+ channels

Lesage

Hibino

Hudspeth

2003

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

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, and neurons contributes to rapid repolarization of the membrane after excitation. Ca 2؉ channels have been shown to bind to a large set of synaptic proteins, but the proteins interacting with Ca 2؉ -activated K ؉ channels remain unknown. Here, we report that the large-conductance Ca 2؉ -activated K ؉ channel of the chicken's cochlear hair cell interacts with ␤-catenin. Yeast two-hybrid assays identified the S10 region of the K ؉ channel's ␣-subunit and the ninth armadillo repeat and carboxyl terminus of ␤-catenin as necessary for the interaction. An antiserum directed against the ␣-subunit specifically coprecipitated ␤-catenin from brain synaptic proteins. ␤-Catenin is known to associate with the synaptic protein Lin7͞Velis͞MALS, whose interaction partner Lin2͞CASK also binds voltage-gated Ca 2؉ channels. ␤-Catenin may therefore provide a physical link between the two types of channels at the presynaptic active zone.T he hair cell, the sensory receptor of the internal ear, releases neurotransmitter at presynaptic active zones studding its basolateral membrane surface (for a review, see ref. 1). Examination of hair cells by loose-seal patch recording demonstrated that each active zone bears a cluster of voltage-gated Ca 2ϩ (Ca V ) channels and Ca 2ϩ -activated K ϩ (K Ca ) channels (2-4). When Ca V channels are activated by a hair cell's depolarization in response to acoustical stimulation, the resultant Ca 2ϩ influx not only triggers synaptic-vesicle release but also opens K Ca channels. The efflux of K ϩ through these channels causes a rapid repolarization that plays a key role in the electrical oscillation that tunes some hair cells (5) and in fast inhibitory synaptic transmission (6). Nerve terminals of the central and peripheral nervous system, including those at the neuromuscular junction, use a similar mechanism to effect repolarization in anticipation of the next action potential (7-11). The presynaptic colocalization of K Ca channels with Ca V channels is thus indispensable for normal electrical signaling by excitatory cells.Electrophysiological and molecular-biological analyses have shown that hair cells express L-type Ca V channels and largeconductance (BK or Maxi) K Ca channels (12-15) that contain, respectively, ␣ 1D -subunits (16-18) and slowpoke (slo) ␣-and slo ␤-subunits (19-22). In hippocampal neurons, both large-and small-conductance K ϩ channels occur in presynaptic regions and are associated, respectively, with L-and N-type Ca V channels (7, 23). The Ca V channels at the presynaptic active zone form a protein complex with several anchoring proteins (24-26), such as Mint-1, CASK, and Rab3-interacting molecule (RIM) binding proteins (RBP). In Drosophila, two cytosolic regulatory proteins, Slob and dSLIP, and two protein kinases, Src and PKAc, are able to assemble with the slo ␣-subunit (27-29). In vertebrates, however, only kinases, such as Src and Syk, have been reported to interact with this subunit (30-32). To seek other proteins that associate with K Ca channels and mediate their presynapti...

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Slob, a Novel Protein that Interacts with the Slowpoke Calcium-Dependent Potassium Channel

Cited by 109 publications

References 51 publications

Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

Identification and Characterization of a SUMO-1 Conjugation System That Modifies Neuronal Calcium/Calmodulin-dependent Protein Kinase II in Drosophila melanogaster

Association of β-catenin with the α-subunit of neuronal large-conductance Ca ²⁺ -activated K+ channels

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Slob, a Novel Protein that Interacts with the Slowpoke Calcium-Dependent Potassium Channel

Cited by 109 publications

References 51 publications

Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels

Identification and Characterization of a SUMO-1 Conjugation System That Modifies Neuronal Calcium/Calmodulin-dependent Protein Kinase II in Drosophila melanogaster

Association of β-catenin with the α-subunit of neuronal large-conductance Ca 2+ -activated K+ channels

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Association of β-catenin with the α-subunit of neuronal large-conductance Ca ²⁺ -activated K+ channels