Document Detail

Antagonistic control of lysosomal fusion by Rab14 and the Lyst-related protein LvsB.
MedLine Citation:
PMID:  23387437     Owner:  NLM     Status:  MEDLINE    
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.
Elena Kypri; Kristin Falkenstein; Arturo De Lozanne
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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.
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MeSH Terms
Biological Transport
Dictyostelium / metabolism*
Endosomes / metabolism
Green Fluorescent Proteins / metabolism
Heterocyclic Compounds with 4 or More Rings / metabolism
Lysosomes / metabolism*
Plasmids / metabolism
Protozoan Proteins / metabolism*
Vesicular Transport Proteins / metabolism*
rab GTP-Binding Proteins / metabolism*
Grant Support
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

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