دورية أكاديمية
Biogenesis of lysosome-related organelles complex-2 is an evolutionarily ancient proto-coatomer complex.
| العنوان: | Biogenesis of lysosome-related organelles complex-2 is an evolutionarily ancient proto-coatomer complex. |
|---|---|
| المؤلفون: | Thomason PA; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Electronic address: p.thomason@crukscotlandinstitute.ac.uk., Corbyn R; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Lilla S; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Sumpton D; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Gilbey T; Cancer Research UK Scotland Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Insall RH; School of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, UK; Division of Cell & Developmental Biology, University College London, London WC1E 6BT, UK. Electronic address: r.insall@ucl.ac.uk. |
| المصدر: | Current biology : CB [Curr Biol] 2024 Aug 05; Vol. 34 (15), pp. 3564-3581.e6. Date of Electronic Publication: 2024 Jul 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: England NLM ID: 9107782 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0445 (Electronic) Linking ISSN: 09609822 NLM ISO Abbreviation: Curr Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: London, UK : Current Biology Ltd., c1991- |
| مواضيع طبية MeSH: | Dictyostelium*/genetics , Dictyostelium*/metabolism , Lysosomes*/metabolism , Protozoan Proteins*/genetics , Protozoan Proteins*/metabolism, Animals ; Evolution, Molecular ; Coatomer Protein/genetics ; Coatomer Protein/metabolism ; Hermanski-Pudlak Syndrome/genetics ; Hermanski-Pudlak Syndrome/metabolism |
| مستخلص: | 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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: BLOC-2; Dictyostelium; WASH; Weibel-Palade bodies; lysosome; lysosome-related organelle; melanosome; proto-coatomer |
| المشرفين على المادة: | 0 (Protozoan Proteins) 0 (Coatomer Protein) |
| تواريخ الأحداث: | Date Created: 20240726 Date Completed: 20240806 Latest Revision: 20240806 |
| رمز التحديث: | 20240807 |
| DOI: | 10.1016/j.cub.2024.06.081 |
| PMID: | 39059394 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1879-0445 |
|---|---|
| DOI: | 10.1016/j.cub.2024.06.081 |