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Biogenesis of lysosome-related organelles complex-2 is an evolutionarily ancient proto-coatomer complex.
- Source :
-
Current Biology . Aug2024, Vol. 34 Issue 15, p3564-3564. 1p. - Publication Year :
- 2024
-
Abstract
- Hermansky-Pudlak syndrome (HPS) is an inherited disorder of intracellular vesicle trafficking affecting the function of lysosome-related organelles (LROs). At least 11 genes underlie the disease, encoding four protein complexes, of which biogenesis of lysosome-related organelles complex-2 (BLOC-2) is the last whose molecular action is unknown. We find that the unicellular eukaryote Dictyostelium unexpectedly contains a complete BLOC-2, comprising orthologs of the mammalian subunits HPS3, -5, and -6, and a fourth subunit, an ortholog of the Drosophila LRO-biogenesis gene, Claret. Lysosomes from Dictyostelium BLOC-2 mutants fail to mature, similar to LROs from HPS patients, but for all endolysosomes rather than a specialized subset. They also strongly resemble lysosomes from WASH mutants. Dictyostelium BLOC-2 localizes to the same compartments as WASH, and in BLOC-2 mutants, WASH is inefficiently recruited, accounting for their impaired lysosomal maturation. BLOC-2 is recruited to endolysosomes via its HPS3 subunit. Structural modeling suggests that all four subunits are proto-coatomer proteins, with important implications for BLOC-2's molecular function. The discovery of Dictyostelium BLOC-2 permits identification of orthologs throughout eukaryotes. BLOC-2 and lysosome-related organelles, therefore, pre-date the evolution of Metazoa and have broader and more conserved functions than previously thought. [Display omitted] • Dictyostelium BLOC-2 comprises orthologs of the mammalian subunits, plus Claret • BLOC-2 mutants have disrupted endolysosome maturation, leading to delayed exocytosis • BLOC-2 functions at the same compartment as WASH, but genetically upstream • BLOC-2 subunit genes are found in diverse eukaryotes but may have been widely lost Thomason et al. discover that biogenesis of lysosome-related organelles complex-2 (BLOC-2) is an ancient proto-coatomer complex widely conserved throughout eukaryotes. In the unicellular Dictyostelium , it functions in a central endolysosomal vesicle maturation pathway, perhaps reflective of its role in the last eukaryotic common ancestor. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DICTYOSTELIUM
*LYSOSOMES
*EXOCYTOSIS
*ORGANELLES
*STRUCTURAL models
Subjects
Details
- Language :
- English
- ISSN :
- 09609822
- Volume :
- 34
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Current Biology
- Publication Type :
- Academic Journal
- Accession number :
- 178786893
- Full Text :
- https://doi.org/10.1016/j.cub.2024.06.081