The Cytoplasmic Tail of Large Conductance, Voltage- and Ca2+-activated K+ (MaxiK) Channel Is Necessary for Its Cell Surface Expression

Wang, Shao Xiong; Ikeda, Masahiro; Guggino, William B.

doi:10.1074/jbc.m208411200

Cited by 32 publications

(42 citation statements)

References 62 publications

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“…All three Slo1 expression constructs contain an N-terminal (ectofacial) myc tag. Placing a myc tag in this position has previously been shown to have minimal effects on gating and trafficking of BK Ca channels (Meera et al, 1997;Wang et al, 2003). HEK293T cells expressing these channels were lysed, and Slo1 channels were immunoprecipitated, in this case using an antibody against the myc tags.…”

Section: Resultsmentioning

confidence: 99%

“…The Slo1 gene, known as KCNMA1 in humans, encodes the pore-forming subunits of BK Ca channels, and it is expressed in a large number (Ն20) of different splice variants that in many cases exhibit substantially different gating properties (Shipston, 2001). Most variants exhibit high levels of constitutive trafficking to the plasma membrane in heterologous expression systems, but some variants are largely retained in intracellular compartments (Zarei et al, 2001;Wang et al, 2003;Kim et al, 2007b,c;Ma et al, 2007). These observations have allowed identification of sequence motifs that play a role in regulating the trafficking of various Slo1 isoforms.…”

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confidence: 99%

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A Novel Actin-Binding Domain on Slo1 Calcium-Activated Potassium Channels Is Necessary for Their Expression in the Plasma Membrane

Zou

Jha²,

Kim³

et al. 2007

Mol Pharmacol

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Large-conductance Ca 2ϩ -activated K ϩ (BK Ca ) channels regulate the physiological properties of many cell types. The gating properties of BK Ca channels are Ca 2ϩ -, voltage-and stretchsensitive, and stretch-sensitive gating of these channels requires interactions with actin microfilaments subjacent to the plasma membrane. Moreover, we have previously shown that trafficking of BK Ca channels to the plasma membrane is associated with processes that alter cytoskeletal dynamics. Here, we show that the Slo1 subunits of BK Ca channels contain a novel cytoplasmic actin-binding domain (ABD) close to the C terminus, considerably downstream from regions of the channel molecule that play a major role in determining channelgating properties. Binding of actin to the ABD can occur in a binary mixture in the absence of other proteins. Coexpression of a small ABD-green fluorescent protein fusion protein that competes with full-length Slo1 channels for binding to actin markedly suppresses trafficking of full-length Slo1 channels to the plasma membrane. In addition, Slo1 channels containing deletions of the ABD that eliminate actin binding are retained in intracellular pools, and they are not expressed on the cell surface. At least one point mutation within the ABD (L1020A) reduces surface expression of Slo1 channels to approximately 25% of wild type, but it does not cause a marked effect on the gating of point mutant channels that reach the cell surface. These data suggest that Slo1-actin interactions are necessary for normal trafficking of BK Ca channels to the plasma membrane and that the mechanisms of this interaction may be different from those that underlie F-actin and stretch-sensitive gating.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

A Novel Actin-Binding Domain on Slo1 Calcium-Activated Potassium Channels Is Necessary for Their Expression in the Plasma Membrane

Zou

Jha²,

Kim³

et al. 2007

Mol Pharmacol

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“…The ␣-subunit of Maxi K channels contains seven transmembrane domains (from S 0 to S 6 ), a short extracellular N terminus, and a long intracellular C terminus (49). The C terminus of the Maxi K ␣-subunit contains four hydrophobic segments (32) and a calcium sensor which affects channel gating (39).…”

Section: Discussionmentioning

confidence: 99%

WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism

Zhuang

Zhang

Wang

et al. 2011

American Journal of Physiology-Renal Physiology

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[with no lysine (k)] kinase is a serine/threonine kinase subfamily. Mutations in two of the WNK kinases result in pseudohypoaldosteronism type II (PHA II) characterized by hypertension, hyperkalemia, and metabolic acidosis. Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity. However, little is known about the effect of WNK kinases on Maxi K, a large-conductance Ca 2ϩ and voltage-activated potassium (K) channel. Here, we report that WNK4 wild-type (WT) significantly inhibits Maxi K channel activity in HEK ␣BK stable cell lines compared with the control group. However, a WNK4 dead-kinase mutant, D321A, has no inhibitory effect on Maxi K activity. We further found that WNK4 inhibits total and cell surface protein expression of Maxi K equally compared with control groups. A dominant-negative dynamin mutant, K44A, did not alter the WNK4-mediated inhibitory effect on Maxi K surface expression. Treatment with bafilomycin A1 (a proton pump inhibitor) and leupeptin (a lysosomal inhibitor) reversed WNK4 WT-mediated inhibition of Maxi K total protein expression. These findings suggest that WNK4 WT inhibits Maxi K activity by reducing Maxi K protein at the membrane, but that the inhibition is not due to an increase in clathrin-mediated endocytosis of Maxi K, but likely due to enhancing its lysosomal degradation. Also, WNK4's inhibitory effect on Maxi K activity is dependent on its kinase activity. protein expression; lysosomal degradation WNK [WITH NO LYSINE (K)] KINASE belongs to a subfamily of serine/threonine kinases (55). Mutations in two members of this family, WNK1 and WNK4, result in pseudohypoaldosteronism type II (PHA II). PHA II, also referred to as Gordon's syndrome, is an autosomal dominant disorder, characterized by hypertension, hyperkalemia, and metabolic acidosis (51). This clinical phenotype suggests that WNK kinases might regulate renal potassium (K) channels, such as renal outer medullary potassium channel (ROMK) or Maxi K channels (BK channels) that are responsible for K handling by the distal nephron. A number of studies indicate that WNK kinases constitute a novel signaling pathway that is involved in the regulation of different ion transporters and channels controlling sodium and K homeostasis (23). In kidney tissue, there are two types of apical K channels identified in the distal nephron by patchclamp analysis (38). One type of K channel is a low-conductance secretory K (SK) channel that has high open probability at resting membrane potential and mediates K ϩ secretion under basal conditions. The properties of the SK channel are consistent with those of ROMK. The other type of K channel has a high single-channel conductance (Ͼ100 pS) and channel kinetics similar to Maxi K channels (34). Although it is generally accepted that ROMK is the K ϩ secretory channel in the mammalian distal nephron, recent in vitro and in vivo studies have provided evidence that Maxi K can also serves as a K ϩ secretory channel in renal tubules (37) and that it plays an important role in K ϩ secretion in ROM...

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“…Apical sorting signals are encoded not only in the amino acid sequence of extracellular, transmembrane, and cytoplasmic domains but also in carbohydrate moieties including N-and O-glycosylations and glycosylphosphatidylinositol anchors (9). Previously we examined the differences in subcellular localization of two splicing variants and showed that the cytoplasmic tail of the renal MaxiK channel is necessary for its cell-surface expression (17). We also found that the renal MaxiK channel is predominantly localized to the apical membrane domain in polarized renal epithelial cells (17).…”

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confidence: 99%

Multiple sequences in the C terminus of MaxiK channels are involved in expression, movement to the cell surface, and apical localization

Kwon

Guggino

2004

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

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Apical expression of the large-conductance, calcium-and voltageactivated potassium (MaxiK) channel in the cortical collecting duct is responsible for flow-stimulated potassium secretion. Here, we identify two cytoplasmic regions controlling apical expression of the MaxiK channel. Disruption of the proximal region results in the intracellular retention of the MaxiK channel without affecting channel assembly, thereby reducing surface expression. Coexpression of the WT channel with this mutant results in a reduction of WT MaxiK channel at the cell surface. Our data indicate that this proximal region is necessary for export of the MaxiK channel from the endoplasmic reticulum as a way to assess the final assembly of the channel. Deletion of a more distal region disrupts apical sorting, resulting in a nonpolarized distribution of the channel without impairing its surface delivery. In summary, we have found that sequences of amino acids in the C terminus of the MaxiK channel operate after the channel is assembled into a multimer and play a role in its expression, movement to the cell surface, and apical localization.

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The Cytoplasmic Tail of Large Conductance, Voltage- and Ca2+-activated K+ (MaxiK) Channel Is Necessary for Its Cell Surface Expression

Cited by 32 publications

References 62 publications

A Novel Actin-Binding Domain on Slo1 Calcium-Activated Potassium Channels Is Necessary for Their Expression in the Plasma Membrane

A Novel Actin-Binding Domain on Slo1 Calcium-Activated Potassium Channels Is Necessary for Their Expression in the Plasma Membrane

WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism

Multiple sequences in the C terminus of MaxiK channels are involved in expression, movement to the cell surface, and apical localization

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