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.
Highlights
Oogenesis prepares the egg to start the development of a new organism
We take advantage of zebrafish genetics and its oocytes with their high vesicle trafficking activity to describe a novel role for the SPASTIZIN homolog Souffle
We show that during zebrafish oogenesis Suf/Spastizin is essential for the maturation of secretory granules
Summary
Oogenesis prepares the egg to start the development of a new organism. During their development, oocytes actively import and secrete proteins using the basic cellular mechanism of vesicle transport [1,2,3]. A plethora of novel regulators were discovered by exploiting the genetics of the Caenorhabditis elegans oocyte [5,6,7,8,9]. Oogenesis starts with a burst of secretory vesicle formation, which are called cortical granules [10,11]. The zebrafish oocyte provides the opportunity to integrate vertebrate genetics to visualize active trafficking of abundant and large vesicles in one big cell
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