Souffle/Spastizin controls secretory vesicle maturation during zebrafish oogenesis
During oogenesis, the egg prepares for fertilization and early embryogenesis. As a consequence, vesicle transport is very active during vitellogenesis, and oocytes are an outstanding system to study regulators of membrane trafficking. Here, we combine zebrafish genetics and the oocyte model to ident...
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Published in | PLoS genetics Vol. 10; no. 6; p. e1004449 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.06.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | During oogenesis, the egg prepares for fertilization and early embryogenesis. As a consequence, vesicle transport is very active during vitellogenesis, and oocytes are an outstanding system to study regulators of membrane trafficking. Here, we combine zebrafish genetics and the oocyte model to identify the molecular lesion underlying the zebrafish souffle (suf) mutation. We demonstrate that suf encodes the homolog of the Hereditary Spastic Paraplegia (HSP) gene SPASTIZIN (SPG15). We show that in zebrafish oocytes suf mutants accumulate Rab11b-positive vesicles, but trafficking of recycling endosomes is not affected. Instead, we detect Suf/Spastizin on cortical granules, which undergo regulated secretion. We demonstrate genetically that Suf is essential for granule maturation into secretion competent dense-core vesicles describing a novel role for Suf in vesicle maturation. Interestingly, in suf mutants immature, secretory precursors accumulate, because they fail to pinch-off Clathrin-coated buds. Moreover, pharmacological inhibition of the abscission regulator Dynamin leads to an accumulation of immature secretory granules and mimics the suf phenotype. Our results identify a novel regulator of secretory vesicle formation in the zebrafish oocyte. In addition, we describe an uncharacterized cellular mechanism for Suf/Spastizin activity during secretion, which raises the possibility of novel therapeutic avenues for HSP research. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. Conceived and designed the experiments: PK AGS RD. Performed the experiments: PK AGS DR CS JC NV RD. Analyzed the data: PK AGS RD. Wrote the paper: PK RD. Current address: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 855 Nutrition et Cerveau, Faculté de Medecine Lyon-Est, Lyon, France |
ISSN: | 1553-7404 1553-7390 1553-7404 |
DOI: | 10.1371/journal.pgen.1004449 |