An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species.
The C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these...
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Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4160200?pdf=render |
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author | Clara L Oeste Mario Pinar Kay O Schink Javier Martínez-Turrión Harald Stenmark Miguel A Peñalva Dolores Pérez-Sala |
author_facet | Clara L Oeste Mario Pinar Kay O Schink Javier Martínez-Turrión Harald Stenmark Miguel A Peñalva Dolores Pérez-Sala |
author_sort | Clara L Oeste |
collection | DOAJ |
description | The C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these selective associations is limited. Here we show, using advanced microscopy, that the isoprenylation and palmitoylation motif of human RhoB (-CINCCKVL) targets chimeric proteins to intraluminal vesicles of endolysosomes in human cells, displaying preferential co-localization with components of the late endocytic pathway. Moreover, this distribution is conserved in distant species, including cells from amphibians, insects and fungi. Blocking lipidic modifications results in accumulation of CINCCKVL chimeras in the cytosol, from where they can reach endolysosomes upon release of this block. Remarkably, CINCCKVL constructs are sorted to intraluminal vesicles in a cholesterol-dependent process. In the lower species, neither the C-terminal sequence of RhoB, nor the endosomal distribution of its homologs are conserved; in spite of this, CINCCKVL constructs also reach endolysosomes in Xenopus laevis and insect cells. Strikingly, this behavior is prominent in the filamentous ascomycete fungus Aspergillus nidulans, in which GFP-CINCCKVL is sorted into endosomes and vacuoles in a lipidation-dependent manner and allows monitoring endosomal movement in live fungi. In summary, the isoprenylated and palmitoylated CINCCKVL sequence constitutes a specific structure which delineates an endolysosomal sorting strategy operative in phylogenetically diverse organisms. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-14T00:56:19Z |
publishDate | 2014-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-7b33b3aa711644969a46dd3d54e503ad2022-12-22T02:21:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10719010.1371/journal.pone.0107190An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species.Clara L OesteMario PinarKay O SchinkJavier Martínez-TurriónHarald StenmarkMiguel A PeñalvaDolores Pérez-SalaThe C-terminal ends of small GTPases contain hypervariable sequences which may be posttranslationally modified by defined lipid moieties. The diverse structural motifs generated direct proteins towards specific cellular membranes or organelles. However, knowledge on the factors that determine these selective associations is limited. Here we show, using advanced microscopy, that the isoprenylation and palmitoylation motif of human RhoB (-CINCCKVL) targets chimeric proteins to intraluminal vesicles of endolysosomes in human cells, displaying preferential co-localization with components of the late endocytic pathway. Moreover, this distribution is conserved in distant species, including cells from amphibians, insects and fungi. Blocking lipidic modifications results in accumulation of CINCCKVL chimeras in the cytosol, from where they can reach endolysosomes upon release of this block. Remarkably, CINCCKVL constructs are sorted to intraluminal vesicles in a cholesterol-dependent process. In the lower species, neither the C-terminal sequence of RhoB, nor the endosomal distribution of its homologs are conserved; in spite of this, CINCCKVL constructs also reach endolysosomes in Xenopus laevis and insect cells. Strikingly, this behavior is prominent in the filamentous ascomycete fungus Aspergillus nidulans, in which GFP-CINCCKVL is sorted into endosomes and vacuoles in a lipidation-dependent manner and allows monitoring endosomal movement in live fungi. In summary, the isoprenylated and palmitoylated CINCCKVL sequence constitutes a specific structure which delineates an endolysosomal sorting strategy operative in phylogenetically diverse organisms.http://europepmc.org/articles/PMC4160200?pdf=render |
spellingShingle | Clara L Oeste Mario Pinar Kay O Schink Javier Martínez-Turrión Harald Stenmark Miguel A Peñalva Dolores Pérez-Sala An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. PLoS ONE |
title | An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. |
title_full | An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. |
title_fullStr | An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. |
title_full_unstemmed | An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. |
title_short | An isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species. |
title_sort | isoprenylation and palmitoylation motif promotes intraluminal vesicle delivery of proteins in cells from distant species |
url | http://europepmc.org/articles/PMC4160200?pdf=render |
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