Linked Life Data

11792815

Source:http://linkedlifedata.com/resource/pubmed/id/11792815

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 24
pubmed:dateCreated
2002-1-16
pubmed:abstractText
The functioning of the endocytic pathway is influenced by a distinct set of rab GTPases, including rab5a, which regulates homotypic fusion of early endosomes. Expression of a dominant active, GTPase-defective rab5a accelerates endosome fusion, causing the formation of a greatly enlarged endocytic compartment. Here we present evidence that rab5a also regulates trafficking between endosomes and lysosomes and may play a role in lysosome biogenesis. The GTPase defective rab5aQ79L mutant was inducibly expressed as an EGFP fusion in HEK293 cells, and the distribution of lysosome proteins and endocytic markers then assessed by deconvolution fluorescence microscopy. During expression of EGFP-rab5aQ79L, the lysosome proteins LAMP-1, LAMP-2 and cathepsin D were found in dilated EGFP-rab5aQ79L-positive vesicles, which also rapidly labeled with transferrin Texas Red. Exogenous tracers that normally traffic to lysosomes after prolonged chase (dextran Texas Red and DiI-LDL) also accumulated in these vesicles. Dextran Texas Red preloaded into lysosomes localized with subsequently expressed EGFP-rab5a Q79L, suggesting the existence of lysosome to endosome traffic. Cells expressing EGFP-rab5a wt or the dominant negative EGFP-rab5aS34N did not exhibit these abnormalities. Despite the dramatic alterations in lysosome protein distribution caused by expression of EGFP-rab5a Q79L, there was little change in the endocytosis or recycling of a cell-surface receptor (beta2-adrenergic receptor). However, there was a deficiency of dense beta-hexosaminidase-containing lysosomes in cells expressing EGFP-rab5aQ79L, as assessed by Percoll gradient fractionation. These results suggest that expression of a GTPase-defective rab5a affects lysosome biogenesis by alteration of traffic between lysosomes and endosomes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4499-508
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11792815-Cell Line, pubmed-meshheading:11792815-Dextrans, pubmed-meshheading:11792815-Endocytosis, pubmed-meshheading:11792815-Endosomes, pubmed-meshheading:11792815-Fluorescent Dyes, pubmed-meshheading:11792815-Gene Expression Regulation, pubmed-meshheading:11792815-Genetic Vectors, pubmed-meshheading:11792815-Glutamine, pubmed-meshheading:11792815-Green Fluorescent Proteins, pubmed-meshheading:11792815-Humans, pubmed-meshheading:11792815-Hydrolysis, pubmed-meshheading:11792815-Leucine, pubmed-meshheading:11792815-Luminescent Proteins, pubmed-meshheading:11792815-Lysosomes, pubmed-meshheading:11792815-Mutagenesis, Site-Directed, pubmed-meshheading:11792815-Protein Transport, pubmed-meshheading:11792815-Xanthenes, pubmed-meshheading:11792815-beta-N-Acetylhexosaminidases, pubmed-meshheading:11792815-rab5 GTP-Binding Proteins
pubmed:year
2001
pubmed:articleTitle
Lysosome proteins are redistributed during expression of a GTP-hydrolysis-defective rab5a.
pubmed:affiliation
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.