Self-Assembly of VPS41 Promotes Sorting Required for Biogenesis of the Regulated Secretory Pathway

Asensio, Cédric S.; Sirkis, Daniel W.; Maas, James W.; Egami, Kiyoshi; To, Tsz-Leung; Brodsky, Frances M.; Shu, Xiaokun; Cheng, Yifan; Edwards, Robert H.

doi:10.1016/j.devcel.2013.10.007

Cited by 78 publications

(102 citation statements)

References 53 publications

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“…More cortical granules were visible in suf / spastizin oocytes (Figures 6A and S5A). Interestingly, their electron dense core was not visible, which is a remarkably strong phenotype compared to other factors involved in dense-core vesicle maturation [75]. We also noted more and smaller lysosomes consistent with the results of the lysotracker staining.…”

Section: Resultssupporting

confidence: 88%

Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis

et al. 2014

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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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Section: Resultssupporting

confidence: 88%

Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis

et al. 2014

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“…In mammalian cells, VPS41 is involved in sorting proteins to the regulated secretory pathway in a process that is also dependent on the CHCR domain, which interacts with adaptor protein 3 (AP-3) (35). This process is highly specific for VPS41 and operates independently of the HOPS complex (35). Therefore, another possibility is that AtVPS41 may also be involved in regulating a secretory pathway independent of the HOPS complex in pollen tubes.…”

Section: Discussionmentioning

confidence: 99%

“…The compromised vacuole biogenesis may affect the buildup of the turgor pressure in vps41 pollen tubes and consequently affects the pollen tube penetration. In mammalian cells, VPS41 is involved in sorting proteins to the regulated secretory pathway in a process that is also dependent on the CHCR domain, which interacts with adaptor protein 3 (AP-3) (35). This process is highly specific for VPS41 and operates independently of the HOPS complex (35).…”

Section: Discussionmentioning

confidence: 99%

AtVPS41-mediated endocytic pathway is essential for pollen tube–stigma interaction inArabidopsis

Hao

Liu

Zhong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In flowering plants, extensive male–female interactions are required for successful fertilization in which various signaling cascades are involved. Prevacuolar compartments (PVC) and vacuoles are two types of subcellular compartments that terminate signal transduction by sequestrating signaling molecules in yeast and mammalian cells; however, the manner in which they might be involved in male–female interactions in plants is unknown. In this study, we identified Arabidopsisthaliana vacuolar protein sorting 41 (AtVPS41), encoded by a single-copy gene with sequence similarity to yeast Vps41p, as a new factor controlling pollen tube–stigma interaction. Loss of AtVPS41 function disrupted penetration of pollen tubes into the transmitting tissue and thus led to failed male transmission. In the pollen tubes, AtVPS41 protein is associated with PVCs and the tonoplast. We demonstrate that AtVPS41 is required for the late stage of the endocytic pathway (i.e., endomembrane trafficking from PVCs to vacuoles) because internalization of cell-surface molecules was normal in the vps41-deficient pollen tubes, whereas PVC-to-vacuole trafficking was impaired. We further show that the CHCR domain is required for subcellular localization and biological functioning of AtVPS41. These results indicate that the AtVPS41-mediated late stage of the endocytic pathway is essential for pollen tube–stigma interaction in Arabidopsis.

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“…AP-3 and the HOPS complex interact physically and might act in the same pathway in regulating endosomal trafficking (Angers and Merz, 2009;Rehling et al, 1999;Wilkin et al, 2008). Knockdown of VPS41 (a HOPS subunit) in PC12 cells leads to similar defects of LDCVs as in AP-3-deficient cells (Asensio et al, 2013). Similarly, the LDCVs in adrenal chromaffin cells from mice deficient in dysbindin [a subunit of biogenesis of lysosome-related organelles complex-1 (BLOC-1)] are reduced in number and increased in vesicle size, leading to reduced secretion events and increased quantal size (Chen et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells

Hao

Wei

Feng

et al. 2015

Journal of Cell Science

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The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky-Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and mutedknockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs.

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Self-Assembly of VPS41 Promotes Sorting Required for Biogenesis of the Regulated Secretory Pathway

Cited by 78 publications

References 53 publications

Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis

Souffle/Spastizin Controls Secretory Vesicle Maturation during Zebrafish Oogenesis

AtVPS41-mediated endocytic pathway is essential for pollen tube–stigma interaction inArabidopsis

Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells

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