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...

Full description

Bibliographic Details
Main Authors: Clara L Oeste, Mario Pinar, Kay O Schink, Javier Martínez-Turrión, Harald Stenmark, Miguel A Peñalva, Dolores Pérez-Sala
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4160200?pdf=render
_version_ 1817990210761261056
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.
first_indexed 2024-04-14T00:56:19Z
format Article
id doaj.art-7b33b3aa711644969a46dd3d54e503ad
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)
record_format Article
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
work_keys_str_mv AT claraloeste anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT mariopinar anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT kayoschink anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT javiermartinezturrion anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT haraldstenmark anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT miguelapenalva anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT doloresperezsala anisoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT claraloeste isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT mariopinar isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT kayoschink isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT javiermartinezturrion isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT haraldstenmark isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT miguelapenalva isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies
AT doloresperezsala isoprenylationandpalmitoylationmotifpromotesintraluminalvesicledeliveryofproteinsincellsfromdistantspecies