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Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria

The molecular motor kinesin is an ATPase that mediates plus end-directed transport of organelles along microtubules. Although the biochemical properties of kinesin are extensively studied, conclusive data on regulation of kinesin-mediated transport are largely lacking. Previously, we showed that the...

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Autores principales: De Vos, Kurt, Severin, Fedor, Van Herreweghe, Franky, Vancompernolle, Katia, Goossens, Vera, Hyman, Anthony, Grooten, Johan
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175118/
https://www.ncbi.nlm.nih.gov/pubmed/10851018
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author De Vos, Kurt
Severin, Fedor
Van Herreweghe, Franky
Vancompernolle, Katia
Goossens, Vera
Hyman, Anthony
Grooten, Johan
author_facet De Vos, Kurt
Severin, Fedor
Van Herreweghe, Franky
Vancompernolle, Katia
Goossens, Vera
Hyman, Anthony
Grooten, Johan
author_sort De Vos, Kurt
collection PubMed
description The molecular motor kinesin is an ATPase that mediates plus end-directed transport of organelles along microtubules. Although the biochemical properties of kinesin are extensively studied, conclusive data on regulation of kinesin-mediated transport are largely lacking. Previously, we showed that the proinflammatory cytokine tumor necrosis factor induces perinuclear clustering of mitochondria. Here, we show that tumor necrosis factor impairs kinesin motor activity and hyperphosphorylates kinesin light chain through activation of two putative kinesin light chain kinases. Inactivation of kinesin, hyperphosphorylation of kinesin light chain, and perinuclear clustering of mitochondria exhibit the same p38 mitogen-activated kinase dependence, indicating their functional relationship. These data provide evidence for direct regulation of kinesin-mediated organelle transport by extracellular stimuli via cytokine receptor signaling pathways.
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spelling pubmed-21751182008-05-01 Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria De Vos, Kurt Severin, Fedor Van Herreweghe, Franky Vancompernolle, Katia Goossens, Vera Hyman, Anthony Grooten, Johan J Cell Biol Original Article The molecular motor kinesin is an ATPase that mediates plus end-directed transport of organelles along microtubules. Although the biochemical properties of kinesin are extensively studied, conclusive data on regulation of kinesin-mediated transport are largely lacking. Previously, we showed that the proinflammatory cytokine tumor necrosis factor induces perinuclear clustering of mitochondria. Here, we show that tumor necrosis factor impairs kinesin motor activity and hyperphosphorylates kinesin light chain through activation of two putative kinesin light chain kinases. Inactivation of kinesin, hyperphosphorylation of kinesin light chain, and perinuclear clustering of mitochondria exhibit the same p38 mitogen-activated kinase dependence, indicating their functional relationship. These data provide evidence for direct regulation of kinesin-mediated organelle transport by extracellular stimuli via cytokine receptor signaling pathways. The Rockefeller University Press 2000-06-12 /pmc/articles/PMC2175118/ /pubmed/10851018 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
De Vos, Kurt
Severin, Fedor
Van Herreweghe, Franky
Vancompernolle, Katia
Goossens, Vera
Hyman, Anthony
Grooten, Johan
Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
title Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
title_full Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
title_fullStr Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
title_full_unstemmed Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
title_short Tumor Necrosis Factor Induces Hyperphosphorylation of Kinesin Light Chain and Inhibits Kinesin-Mediated Transport of Mitochondria
title_sort tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175118/
https://www.ncbi.nlm.nih.gov/pubmed/10851018
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