Document Detail


Antagonistic control of lysosomal fusion by Rab14 and the Lyst-related protein LvsB.
MedLine Citation:
PMID:  23387437     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
While loss of the protein Lyst causes abnormal lysosomes in patients with Chediak-Higashi syndrome, the contribution of Lyst to lysosome biology is not known. Previously we found that the Dictyostelium ortholog of Lyst, LvsB, is a cytosolic protein that associates with lysosomes and post-lysosomes to prevent their inappropriate fusion. Here we provide three lines of evidence that indicate that LvsB contributes to lysosome function by antagonizing the function of DdRab14, a protein that promotes homotypic fusion among lysosomes. (1) Instead of restricting DdRab14 to lysosomes, cells that lack LvsB expand DdRab14 localization to include post-lysosomes. (2) Expression of activated DdRab14 phenocopies the loss of LvsB, causing inappropriate heterotypic fusion between lysosomes and post-lysosomes and their subsequent enlargement. (3) Conversely, expression of inactivated DdRab14 suppresses the phenotype of LvsB null cells and restores their lysosomal size and segregation from post-lysosomes. Our data suggest a scenario where LvsB binds to late lysosomes and promotes the inactivation of DdRab14. This inactivation allows the lysosomes to mature into post-lysosomes for eventual secretion. We propose that human Lyst may function similarly to regulate Rab-dependent fusion of lysosomal compartments.
Authors:
Elena Kypri; Kristin Falkenstein; Arturo De Lozanne
Related Documents :
23980007 - Measuring the dynamics of chromatin proteins during differentiation.
23248297 - Spatiotemporal analysis of organelle and macromolecular complex inheritance.
23319327 - Shotgun proteomics study of early biofilm formation process of acidithiobacillus ferroo...
23906917 - Bimolecular fluorescence complementation (bifc) analysis of protein interactions in liv...
12399017 - Polymorphism at codon 174 of the prion-like protein gene is not associated with sporadi...
22677627 - Selective n-terminal fluorescent labeling of proteins using nbd-cl: a method to disting...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-12
Journal Detail:
Title:  Traffic (Copenhagen, Denmark)     Volume:  14     ISSN:  1600-0854     ISO Abbreviation:  Traffic     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-09     Completed Date:  2013-12-18     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  100939340     Medline TA:  Traffic     Country:  England    
Other Details:
Languages:  eng     Pagination:  599-609     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons A/S.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Biological Transport
Dictyostelium / metabolism*
Endosomes / metabolism
Green Fluorescent Proteins / metabolism
Heterocyclic Compounds with 4 or More Rings / metabolism
Humans
Lysosomes / metabolism*
Phenotype
Plasmids / metabolism
Protozoan Proteins / metabolism*
Vesicular Transport Proteins / metabolism*
rab GTP-Binding Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
AI078136/AI/NIAID NIH HHS; GM48745/GM/NIGMS NIH HHS; R01 GM048745/GM/NIGMS NIH HHS; R21 AI078136/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Heterocyclic Compounds with 4 or More Rings; 0/LYST protein, human; 0/Protozoan Proteins; 0/Vesicular Transport Proteins; 0/vacuolin-1; 147336-22-9/Green Fluorescent Proteins; EC 3.6.1.-/Rab14 protein, human; EC 3.6.1.-/rab GTP-Binding Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Relationship between urinary fractional excretion of sodium and life prognosis in liver cirrhosis pa...
Next Document:  Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biologic...