LINGO1 is a regulatory subunit of large conductance, Ca
            <sup>2+</sup>
            -activated potassium channels

Dudem, Srikanth; Large, Roddy J.; Kulkarni, Shruti G.; McClafferty, Heather; Tikhonova, Irina G.; Sergeant, Gerard P.; Thornbury, Keith D.; Shipston, Michael J.; Perrino, Brian A.; Hollywood, Mark A.

doi:10.1073/pnas.1916715117

Cited by 42 publications

(38 citation statements)

References 34 publications

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“…These three genes received a non-zero coefficient for the markedly affected group, and two of them ( HS3ST2 , ROBO1) also received a non-zero coefficient for the unaffected group in ENET analysis ( S3 Table ), suggesting these two genes are markers of interest for assessing disease severity. Additionally, the gene encoding leucine rich repeat and Immunoglobin-like domain-containing protein 1 ( LINGO1) which is involved in the modulation of a voltage-gated potassium channel [ 48 ], and inhibition of axon regeneration [ 49 ] was downregulated in the p . major muscle of Wooden Breast-affected chickens [ 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

Evidence of vascular endothelial dysfunction in Wooden Breast disorder in chickens: Insights through gene expression analysis, ultra-structural evaluation and supervised machine learning methods

2021

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Several gene expression studies have been previously conducted to characterize molecular basis of Wooden Breast myopathy in commercial broiler chickens. These studies have generally used a limited sample size and relied on a binary disease outcome (unaffected or affected by Wooden Breast), which are appropriate for an initial investigation. However, to identify biomarkers of disease severity and development, it is necessary to use a large number of samples with a varying degree of disease severity. Therefore, in this study, we assayed a relatively large number of samples (n = 96) harvested from the pectoralis major muscle of unaffected (U), partially affected (P) and markedly affected (A) chickens. Gene expression analysis was conducted using the nCounter MAX Analysis System and data were analyzed using four different supervised machine-learning methods, including support vector machines (SVM), random forests (RF), elastic net logistic regression (ENET) and Lasso logistic regression (LASSO). The SVM method achieved the highest prediction accuracy for both three-class (U, P and A) and two-class (U and P+A) classifications with 94% prediction accuracy for two-class classification and 85% for three-class classification. The results also identified biomarkers of Wooden Breast severity and development. Additionally, gene expression analysis and ultrastructural evaluations provided evidence of vascular endothelial cell dysfunction in the early pathogenesis of Wooden Breast.

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Section: Discussionmentioning

confidence: 99%

Evidence of vascular endothelial dysfunction in Wooden Breast disorder in chickens: Insights through gene expression analysis, ultra-structural evaluation and supervised machine learning methods

2021

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“…There are four subtypes of β subunits (β1-β4) (Bhattarai et al, 2014), and mainly β1 subunit is in vascular smooth muscle cells. In addition to β subunits, recent studies have found that the auxiliary subunits of the BK channel also include the γ subunit and subunit LINGO1, which are rich in leucine repeat sequences (Zhang and Yan, 2014;Dudem et al, 2020). Auxiliary subunits are FIGURE 1 | A schematic figure of the ubiquitin proteasome system.…”

Section: Bk Channel Dysfunction In Diabetic Coronary Arterymentioning

confidence: 99%

BK Channel Dysfunction in Diabetic Coronary Artery: Role of the E3 Ubiquitin Ligases

Qian

Liu

et al. 2020

Front. Physiol.

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Diabetic coronary arterial disease is a leading cause of morbidity and mortality in diabetic patients. The impaired function of large-conductance calcium-activated potassium channels (BK channels) is involved in diabetic coronary arterial disease. Many studies have indicated that the reduced BK channel expression in diabetic coronary artery is attributed to ubiquitin-mediated protein degradation by the ubiquitin-proteasome system. This review focuses on the influence and the mechanisms of BK channel regulation by E3 ubiquitin ligases in diabetic coronary arterial disease. Thus, BK channels regulated by E3 ubiquitin ligase may play a pivotal role in the coronary pathogenesis of diabetic mellitus and, as such, is a potentially attractive target for therapeutic intervention.

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“…BK channel surface expression is attenuated in channels that are deacylated at the S0–S1 loop, as a result of increased retention in the trans-Golgi network ( 15 ). To assay BK channel surface expression, we exploited an on-cell Western approach to assay surface expression of epitope-tagged BK channels in cell population assays ( 16 , 21 ). In these assays, the FLAG epitope at the extracellular N terminus of the BK channel is used to assay channels that are resident at the cell surface in intact cells, whereas the HA epitope at the intracellular C terminus of the channel allows assay of total BK channel expression in the same cells following cell permeabilization.…”

Section: Resultsmentioning

confidence: 99%

Site-specific deacylation by ABHD17a controls BK channel splice variant activity

McClafferty

Runciman

Shipston

2020

Journal of Biological Chemistry

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S-acylation, the reversible post-translational lipid modification of proteins is an important mechanism to control the properties and function of ion channels and other polytopic transmembrane proteins. However, while increasing evidence reveals the role of diverse acyl protein transferases (zDHHC) in controlling ion channel S-acylation the acyl protein thioesterases that control ion channel deacylation are very poorly defined. Here we show that the α/β-hydrolase domain-containing protein 17a (ABHD17a) deacylates the STREX domain of large conductance voltage- and calcium- activated potassium (BK) channels inhibiting channel activity independently of effects on channel surface expression. Importantly, ABHD17a deacylates BK channels in a site- specific manner as it has no effect on the S-acylated S0-S1 domain conserved in all BK channels that controls membrane trafficking and is deacylated by the acyl protein thioesterase Lypla1. Thus, distinct S-acylated domains in the same polytopic transmembrane protein can be regulated by different acyl protein thioesterases revealing mechanisms for generating both specificity and diversity for these important enzymes to control the properties and functions of ion channels.

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LINGO1 is a regulatory subunit of large conductance, Ca ²⁺ -activated potassium channels

Cited by 42 publications

References 34 publications

Evidence of vascular endothelial dysfunction in Wooden Breast disorder in chickens: Insights through gene expression analysis, ultra-structural evaluation and supervised machine learning methods

Evidence of vascular endothelial dysfunction in Wooden Breast disorder in chickens: Insights through gene expression analysis, ultra-structural evaluation and supervised machine learning methods

BK Channel Dysfunction in Diabetic Coronary Artery: Role of the E3 Ubiquitin Ligases

Site-specific deacylation by ABHD17a controls BK channel splice variant activity

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LINGO1 is a regulatory subunit of large conductance, Ca 2+ -activated potassium channels

Cited by 42 publications

References 34 publications

Evidence of vascular endothelial dysfunction in Wooden Breast disorder in chickens: Insights through gene expression analysis, ultra-structural evaluation and supervised machine learning methods

Evidence of vascular endothelial dysfunction in Wooden Breast disorder in chickens: Insights through gene expression analysis, ultra-structural evaluation and supervised machine learning methods

BK Channel Dysfunction in Diabetic Coronary Artery: Role of the E3 Ubiquitin Ligases

Site-specific deacylation by ABHD17a controls BK channel splice variant activity

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LINGO1 is a regulatory subunit of large conductance, Ca ²⁺ -activated potassium channels