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CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content

Mutations in human CEP290 cause cilia-related disorders that range in severity from isolated blindness to perinatal lethality. Here, we describe a Chlamydomonas reinhardtii mutant in which most of the CEP290 gene is deleted. Immunoelectron microscopy indicated that CEP290 is located in the flagellar...

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Autores principales: Craige, Branch, Tsao, Che-Chia, Diener, Dennis R., Hou, Yuqing, Lechtreck, Karl-Ferdinand, Rosenbaum, Joel L., Witman, George B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935561/
https://www.ncbi.nlm.nih.gov/pubmed/20819941
http://dx.doi.org/10.1083/jcb.201006105
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author Craige, Branch
Tsao, Che-Chia
Diener, Dennis R.
Hou, Yuqing
Lechtreck, Karl-Ferdinand
Rosenbaum, Joel L.
Witman, George B.
author_facet Craige, Branch
Tsao, Che-Chia
Diener, Dennis R.
Hou, Yuqing
Lechtreck, Karl-Ferdinand
Rosenbaum, Joel L.
Witman, George B.
author_sort Craige, Branch
collection PubMed
description Mutations in human CEP290 cause cilia-related disorders that range in severity from isolated blindness to perinatal lethality. Here, we describe a Chlamydomonas reinhardtii mutant in which most of the CEP290 gene is deleted. Immunoelectron microscopy indicated that CEP290 is located in the flagellar transition zone in close association with the prominent microtubule–membrane links there. Ultrastructural analysis revealed defects in these microtubule–membrane connectors, resulting in loss of attachment of the flagellar membrane to the transition zone microtubules. Biochemical analysis of isolated flagella revealed that the mutant flagella have abnormal protein content, including abnormal levels of intraflagellar transport proteins and proteins associated with ciliopathies. Experiments with dikaryons showed that CEP290 at the transition zone is dynamic and undergoes rapid turnover. The results indicate that CEP290 is required to form microtubule–membrane linkers that tether the flagellar membrane to the transition zone microtubules, and is essential for controlling flagellar protein composition.
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spelling pubmed-29355612011-03-06 CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content Craige, Branch Tsao, Che-Chia Diener, Dennis R. Hou, Yuqing Lechtreck, Karl-Ferdinand Rosenbaum, Joel L. Witman, George B. J Cell Biol Research Articles Mutations in human CEP290 cause cilia-related disorders that range in severity from isolated blindness to perinatal lethality. Here, we describe a Chlamydomonas reinhardtii mutant in which most of the CEP290 gene is deleted. Immunoelectron microscopy indicated that CEP290 is located in the flagellar transition zone in close association with the prominent microtubule–membrane links there. Ultrastructural analysis revealed defects in these microtubule–membrane connectors, resulting in loss of attachment of the flagellar membrane to the transition zone microtubules. Biochemical analysis of isolated flagella revealed that the mutant flagella have abnormal protein content, including abnormal levels of intraflagellar transport proteins and proteins associated with ciliopathies. Experiments with dikaryons showed that CEP290 at the transition zone is dynamic and undergoes rapid turnover. The results indicate that CEP290 is required to form microtubule–membrane linkers that tether the flagellar membrane to the transition zone microtubules, and is essential for controlling flagellar protein composition. The Rockefeller University Press 2010-09-06 /pmc/articles/PMC2935561/ /pubmed/20819941 http://dx.doi.org/10.1083/jcb.201006105 Text en © 2010 Craige et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Craige, Branch
Tsao, Che-Chia
Diener, Dennis R.
Hou, Yuqing
Lechtreck, Karl-Ferdinand
Rosenbaum, Joel L.
Witman, George B.
CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
title CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
title_full CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
title_fullStr CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
title_full_unstemmed CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
title_short CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
title_sort cep290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935561/
https://www.ncbi.nlm.nih.gov/pubmed/20819941
http://dx.doi.org/10.1083/jcb.201006105
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