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Antagonistic Control of Lysosomal Fusion by Rab14 and the Lyst‐Related Protein LvsB
Author(s) -
Kypri Elena,
Falkenstein Kristin,
De Lozanne Arturo
Publication year - 2013
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12058
Subject(s) - lysosome , microbiology and biotechnology , biology , rab , fusion protein , function (biology) , cytosol , lipid bilayer fusion , biochemistry , enzyme , gtpase , recombinant dna , membrane , gene
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.