title: Souffle/Spastizin controls secretory vesicle maturation during zebrafish oogenesis.
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.
authors: Institut fuer Entwicklungsbiochemie, Georg-August Universitaet Goettingen, Goettingen, Germany.
authors: Palsamy
authors: P
authors: Kanagaraj
authors: Departement de Zoologie et Biologie Animale, Universite de Geneve, Geneva, Switzerland.
authors: Amandine
authors: A
authors: Gautier-Stein
authors: Max-Planck Institut fuer Biophysikalische Chemie, Goettingen, Germany.
authors: Dietmar
authors: D
authors: Riedel
authors: Institut fuer Entwicklungsbiochemie, Georg-August Universitaet Goettingen, Goettingen, Germany.
authors: Christoph
authors: C
authors: Schomburg
authors: IRTA-Institute of Marine Sciences, CSIC, Barcelona, Spain.
authors: Joan
authors: J
authors: Cerdà
authors: Institut fuer Entwicklungsbiochemie, Georg-August Universitaet Goettingen, Goettingen, Germany.
authors: Nadine
authors: N
authors: Vollack
authors: Institut fuer Entwicklungsbiochemie, Georg-August Universitaet Goettingen, Goettingen, Germany; Departement de Zoologie et Biologie Animale, Universite de Geneve, Geneva, Switzerland.
authors: Roland
authors: R
authors: Dosch
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005306:Fertilization / Q000235:genetics; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*; D009866:Oogenesis / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D022142:Secretory Vesicles / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D002352:Carrier Proteins; D029961:Zebrafish Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C528699:ZFYVE26 protein, human; C000600053:zfyve26 protein, zebrafish