Endocytosis of HERG is clathrin-independent and involves arf6.

The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental imp...

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Autores principales:	Rucha Karnik, Melanie J Ludlow, Nada Abuarab, Andrew J Smith, Matthew E L Hardy, David J S Elliott, Asipu Sivaprasadarao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b098201bb4e49979d0c500ef772d6d1
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spelling	oai:doaj.org-article:4b098201bb4e49979d0c500ef772d6d12021-11-18T08:39:12ZEndocytosis of HERG is clathrin-independent and involves arf6.1932-620310.1371/journal.pone.0085630https://doaj.org/article/4b098201bb4e49979d0c500ef772d6d12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24392021/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6.Rucha KarnikMelanie J LudlowNada AbuarabAndrew J SmithMatthew E L HardyDavid J S ElliottAsipu SivaprasadaraoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e85630 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rucha Karnik Melanie J Ludlow Nada Abuarab Andrew J Smith Matthew E L Hardy David J S Elliott Asipu Sivaprasadarao Endocytosis of HERG is clathrin-independent and involves arf6.
description	The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6.
format	article
author	Rucha Karnik Melanie J Ludlow Nada Abuarab Andrew J Smith Matthew E L Hardy David J S Elliott Asipu Sivaprasadarao
author_facet	Rucha Karnik Melanie J Ludlow Nada Abuarab Andrew J Smith Matthew E L Hardy David J S Elliott Asipu Sivaprasadarao
author_sort	Rucha Karnik
title	Endocytosis of HERG is clathrin-independent and involves arf6.
title_short	Endocytosis of HERG is clathrin-independent and involves arf6.
title_full	Endocytosis of HERG is clathrin-independent and involves arf6.
title_fullStr	Endocytosis of HERG is clathrin-independent and involves arf6.
title_full_unstemmed	Endocytosis of HERG is clathrin-independent and involves arf6.
title_sort	endocytosis of herg is clathrin-independent and involves arf6.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4b098201bb4e49979d0c500ef772d6d1
work_keys_str_mv	AT ruchakarnik endocytosisofhergisclathrinindependentandinvolvesarf6 AT melaniejludlow endocytosisofhergisclathrinindependentandinvolvesarf6 AT nadaabuarab endocytosisofhergisclathrinindependentandinvolvesarf6 AT andrewjsmith endocytosisofhergisclathrinindependentandinvolvesarf6 AT matthewelhardy endocytosisofhergisclathrinindependentandinvolvesarf6 AT davidjselliott endocytosisofhergisclathrinindependentandinvolvesarf6 AT asipusivaprasadarao endocytosisofhergisclathrinindependentandinvolvesarf6
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Endocytosis of HERG is clathrin-independent and involves arf6.

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