RGD Reference Report - Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain.

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Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain.
Authors:	Jo, S Lee, KH Song, S Jung, YK Park, CS
Citation:	Jo S, etal., J Neurochem. 2005 Sep;94(5):1212-24. Epub 2005 Jul 25.
RGD ID:	1581583
Pubmed:	PMID:16045448 (View Abstract at PubMed)
DOI:	DOI:10.1111/j.1471-4159.2005.03344.x (Journal Full-text)
Large-conductance Ca2+-activated K+ (BK(Ca)) channels are activated by membrane depolarization and modulated by intracellular Ca2+. Here, we report the direct interaction of cereblon (CRBN) with the cytosolic carboxy-terminus of the BK(Ca) channel alpha subunit (Slo). Rat CRBN contained the N-terminal domain of the Lon protease, a 'regulators of G protein-signaling' (RGS)-like domain, a leucine zipper (LZ) motif, and four putative protein kinase C (PKC) phosphorylation sites. RNA messages of rat cereblon (rCRBN) were widely distributed in different tissues with especially high-levels of expression in the brain. Direct association of rCRBN with the BK(Ca) channel was confirmed by immunoprecipitation in brain lysate, and the two proteins were co-localized in cultured rat hippocampal neurons. Ionic currents evoked by the rSlo channel were dramatically suppressed upon coexpression of rCRBN. rCRBN decreased the formation of the tetrameric rSlo complex thus reducing the surface expression of functional channels. Therefore, we suggest that CRBN may play an important role in assembly and surface expression of functional BK(Ca) channels by direct interaction with the cytosolic C-terminus of its alpha-subunit.

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Crbn	Rat	negative regulation of monoatomic ion transmembrane transport		IDA			RGD
Crbn	Rat	negative regulation of protein-containing complex assembly		IDA		Kcnma1 homotetramers	RGD
Crbn	Rat	positive regulation of protein-containing complex assembly		IDA		Kcnma1 homodimers	RGD

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Kcnma1	Rat	dendrite		IDA			RGD
Kcnma1	Rat	external side of plasma membrane		IDA			RGD
Kcnma1	Rat	neuronal cell body		IDA			RGD
Crbn	Rat	perinuclear region of cytoplasm		IDA			RGD

Molecular Function

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Kcnma1	Rat	identical protein binding		IPI	Kcnma1 (Rattus norvegicus)	homodimerization and homotetramerization	RGD
Kcnma1	Rat	protein binding		IPI	Crbn (Rattus norvegicus)		RGD
Crbn	Rat	transmembrane transporter binding		IPI	Kcnma1 (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Crbn (cereblon)

Kcnma1 (potassium calcium-activated channel subfamily M alpha 1)

Additional Information

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Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain.