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PLoS Genet. 2014 Jun 26;10(6):e1004449. doi: 10.1371/journal.pgen.1004449. eCollection 2014 Jun.

Souffle/Spastizin controls secretory vesicle maturation during zebrafish oogenesis.

Author information

1
Institut fuer Entwicklungsbiochemie, Georg-August Universitaet Goettingen, Goettingen, Germany.
2
Departement de Zoologie et Biologie Animale, Universite de Geneve, Geneva, Switzerland.
3
Max-Planck Institut fuer Biophysikalische Chemie, Goettingen, Germany.
4
IRTA-Institute of Marine Sciences, CSIC, Barcelona, Spain.
5
Institut fuer Entwicklungsbiochemie, Georg-August Universitaet Goettingen, Goettingen, Germany; Departement de Zoologie et Biologie Animale, Universite de Geneve, Geneva, Switzerland.

Abstract

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.

PMID:
24967841
PMCID:
PMC4072560
DOI:
10.1371/journal.pgen.1004449
[Indexed for MEDLINE]
Free PMC Article

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