Human CLC-K Channels Require Palmitoylation of Their Accessory Subunit Barttin to Be Functional

Steinke, Kim Vanessa; Gorinski, Nataliya; Wojciechowski, Daniel; Todorov, Vladimir; Guseva, Daria; Ponimaskin, Evgeni; Fahlke, Christoph; Fischer, Martin

doi:10.1074/jbc.m114.631705

Cited by 19 publications

(37 citation statements)

References 53 publications

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“…Altogether, the above-mentioned results (i.e., Figs 2, 3 and S3) are in line with our previous observation that non-palmitoylated barttin did not reduce surface membrane insertion of ClC-K/barttin, but selectively impaired activation of the channel complex (8).…”

Section: Knockdown Of Dhhc7 Reduces Activation Of Hclc-ka/barttin Chasupporting

confidence: 92%

“…S3D). The results confirmed the wellknown barttin function of promoting ClC-Ka insertion into the plasma membrane (8). More importantly, manipulation of barttin palmitoylation via DHHC7 overexpression or knockdown did not result in any visible changes in the distribution of the ClC-Ka/barttin complex in MDCKII cells (Figs S3C,D).…”

Section: Dhhc7 Is a Palmitoyl Acyltransferase For Barttin -supporting

confidence: 85%

“…Our previous results demonstrated that palmitoylation of barttin is mandatory for activation of the hClC-K/barttin channel complex, whereas the voltage dependence of activation and plasma membrane integration remained unchanged (8). Therefore, we hypothesized that modulation of barttin palmitoylation by overexpression or knockdown of DHHC7 influences the whole cell current amplitudes of HEK293T cells expressing hClC-Ka/barttin.…”

Section: Knockdown Of Dhhc7 Reduces Activation Of Hclc-ka/barttin Chamentioning

confidence: 95%

“…We recently showed that barttin is palmitoylated both in vivo and in vitro, and identified cysteine residues Cys54 and Cys56 as the palmitoylation sites (8). Expression of palmitoylation-deficient barttin mutants reduced the macroscopic current amplitudes of ClC-K/barttin channels without affecting ClC-K/barttin expression and plasma membrane insertion, demonstrating that barttin palmitoylation is necessary for the activation of plasma membrane-inserted ClC-K/barttin channels (8).…”

Section: Introductionmentioning

confidence: 99%

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DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

Gorinski

Wojciechowski

Guseva

et al. 2020

Journal of Biological Chemistry

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Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this posttranslational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl-https://www.jbc.org/cgi/

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Section: Knockdown Of Dhhc7 Reduces Activation Of Hclc-ka/barttin Chasupporting

confidence: 92%

Section: Dhhc7 Is a Palmitoyl Acyltransferase For Barttin -supporting

confidence: 85%

Section: Knockdown Of Dhhc7 Reduces Activation Of Hclc-ka/barttin Chamentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

Gorinski

Wojciechowski

Guseva

et al. 2020

Journal of Biological Chemistry

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“…Several disease-causing mutations in the cytosolic amino terminus of barttin lack activation of CLC-K channels upon co-expression (26). Recently, it was shown that cysteines at positions 54 and 56, located immediately after the second transmembrane domain of barttin, must be palmitoylated for the activation of CLC-K channels (29). These findings might support a possible interaction of the CBS2 domain of ClC-Kb with the cytosolic amino acids close to the transmembrane core (61).…”

Section: Discussionsupporting

confidence: 56%

Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking

Stölting

Bungert-Plümke

Franzen

et al. 2015

Journal of Biological Chemistry

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Background: Carboxyl-terminal truncations of hClC-Kb cause Bartter syndrome. Results: hClC-Kb channels lacking the carboxyl terminus still associate with barttin, but are neither stabilized in the membrane nor activated. Conclusion: Truncated hClC-Kb channels are not regulated by barttin. Significance: Elucidating the role of the carboxyl terminus of hClC-Kb significantly improves our understanding of CLC-K regulation by barttin.

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Renal Chloride Channels in Relation to Sodium Chloride Transport

Teulon

Planelles

Sepúlveda

et al. 2018

Comprehensive Physiology

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The many mechanisms governing NaCl absorption in the diverse parts of the renal tubule have been largely elucidated, although some of them, as neutral NaCl absorption across the cortical collecting duct or regulation through with‐no‐lysine (WNK) kinases have emerged only recently. Chloride channels, which are important players in these processes, at least in the distal nephron, are the focus of this review. Over the last 20‐year period, experimental studies using molecular, electrophysiological, and physiological/functional approaches have deepened and renewed our views on chloride channels and their role in renal function. Two chloride channels of the ClC family, named as ClC‐Ka and ClC‐Kb in humans and ClC‐K1 and ClC‐K2 in other mammals, are preponderant and play complementary roles: ClC‐K1/Ka is mainly involved in the building of the interstitial cortico‐medullary concentration gradient, while ClC‐K2/Kb participates in NaCl absorption in the thick ascending limb, distal convoluted tubule and the intercalated cells of the collecting duct. The two ClC‐Ks might also be involved indirectly in proton secretion by type A intercalated cells. Other chloride channels in the kidneys include CFTR, TMEM16A, and probably volume‐regulated LRRC8 chloride channels, whose function and molecular identity have not as yet been established. © 2019 American Physiological Society. Compr Physiol 9:301‐342, 2019.

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Human CLC-K Channels Require Palmitoylation of Their Accessory Subunit Barttin to Be Functional

Cited by 19 publications

References 53 publications

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking

Renal Chloride Channels in Relation to Sodium Chloride Transport

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