<i>VPS13</i>Regulates Membrane Morphogenesis During Sporulation in<i>Saccharomyces cerevisiae</i>

Park, Jae-Sook; Neiman, Aaron M.

doi:10.1242/jcs.105114

Cited by 101 publications

(162 citation statements)

References 57 publications

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“…In this context, it has been proposed that the yeast Atg18/Atg2 complex is required to generate negative curvature at the forming autophagosome or fulfi lls an essential function at the elongating tips of the phagophore ( 43 ). Likewise it was recently found that Vps13 regulates membrane bending and promotes the expansion of the prospore membrane in yeast ( 68 ). From this, one would assume that malfunctions of either of the human Atg2/Vps13 proteins should be correlated to distinct human pathologies with defects in intracellular membrane biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells

Pfisterer

Bakula²,

Frickey

et al. 2014

Journal of Lipid Research

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Cellular autophagy is an evolutionarily highly conserved degradation pathway for both stochastic and selective degradation of cytoplasmic cargo within the lysosomal compartment. As such, this process of self-eating secures cellular homeostasis and survival, while malfunction contributes to the initiation and development of many agerelated human diseases including diabetes, tumorigenesis, and neurodegeneration ( 1-4 ). Autophagy is constitutively active on a low basal level resulting in constant cytoplasmic turnover and the specifi c elimination of macromolecule aggregates and damaged organelles. Following a great variety of cellular insults such as nutrient starvation, autophagy is induced above basal level and produces monomers and energy for subsequent recycling processes.Autophagy is hallmarked by the formation of doublemembrane vesicles called autophagosomes that are generated from initial preautophagosomal membrane precursors or phagophores. Elongation of the phagophore and subsequent vesicle closure complete the formation of autophagosomes that sequester the cytoplasmic cargo and communicate with the lysosomal compartment to acquire acidic hydrolases for cargo breakdown ( 5-7 ).Abstract Autophagy is a lysosomal bulk degradation pathway for cytoplasmic cargo, such as long-lived proteins, lipids, and organelles. Induced upon nutrient starvation, autophagic degradation is accomplished by the concerted actions of autophagy-related (ATG) proteins. Here we demonstrate that two ATGs, human Atg2A and Atg14L, colocalize at cytoplasmic lipid droplets (LDs) and are functionally involved in controlling the number and size of LDs in human tumor cell lines. We show that Atg2A is targeted to cytoplasmic ADRP-positive LDs that migrate bidirectionally along microtubules. The LD localization of Atg2A was found to be independent of the autophagic status. Further, Atg2A colocalized with Atg14L under nutrient-rich conditions when autophagy was not induced. Upon nutrient starvation and dependent on phosphatidylinositol 3-phosphate [PtdIns(3)P] generation, both Atg2A and Atg14L were also specifically targeted to endoplasmic reticulum-associated early autophagosomal membranes, marked by the PtdIns(3)P effectors double-FYVE containing protein 1 (DFCP1) and WD-repeat protein interacting with phosphoinositides 1 (WIPI-1) , both of which function at the onset of autophagy. These data provide evidence for additional roles of Atg2A and Atg14L in the formation of early autophagosomal membranes and also in lipid metabolism. -Pfi sterer, S. G., D. Bakula, T. Frickey, A. Cezanne, D. Brigger, M. P. Tschan, H. Robenek, and T. ProikasCezanne. Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells.

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Section: Discussionmentioning

confidence: 99%

Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells

Pfisterer

Bakula²,

Frickey

et al. 2014

Journal of Lipid Research

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“…Moreover, after loss of Vps13p function an in increased cytotoxicity of an expanded polyQ domain in Rnq1p has been detected (10). Recently, Vps13p was shown to be required for prospore membrane morphogenesis through regulation of phosphatidylinositol phosphatases (11,12). Our previous results have established the 450 kDa protein COH1 as an atypical Golgi matrix protein lacking coiled-coil domains that is crucial for Golgi complex organization.…”

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confidence: 82%

Cohen Syndrome-associated Protein COH1 Physically and Functionally Interacts with the Small GTPase RAB6 at the Golgi Complex and Directs Neurite Outgrowth

Seifert

Kühnisch

Maritzen

et al. 2015

Journal of Biological Chemistry

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Background: COH1 is a peripheral membrane protein that is required for Golgi complex integrity and function. Results: Association of COH1 with the Golgi complex is mediated by its interaction with RAB6 and is required for neurite outgrowth. Conclusion: COH1 acts as downstream effector protein of RAB6. Significance: Defective neuronal outgrowth due to loss of COH1 contributes to the neurological impairments found in Cohen syndrome patients.

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“…24,25 In simpler organisms, null mutants in Saccharomyces cerevisiae and Tetrahymena thermophila suggest a role of Vps13 and VPS13A in membrane traffic and phagocytosis respectively but the precise VPS13 function is largely unknown. [26][27][28] Here we describe that the VPS13-related protein TipC is required for efficient autophagy in D. discoideum. We extended our observations to human VPS13A by analyzing autophagy in RNA-interfered HeLa cells.…”

Section: Introductionmentioning

confidence: 90%

TipC and the chorea-acanthocytosis protein VPS13A regulate autophagy inDictyosteliumand human HeLa cells

2015

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Deficient autophagy causes a distinct phenotype in Dictyostelium discoideum, characterized by the formation of multitips at the mound stage. This led us to analyze autophagy in a number of multitipped mutants described previously (tipA(-), tipB(-), tipC(-), and tipD(-)). We found a clear autophagic dysfunction in tipC(-) and tipD(-) while the others showed no defects. tipD codes for a homolog of Atg16, which confirms the role of this protein in Dictyostelium autophagy and validates our approach. The tipC-encoded protein is highly similar to human VPS13A (also known as chorein), whose mutations cause the chorea-acanthocytosis syndrome. No member of the VPS13 protein family has been previously related to autophagy despite the presence of a region of similarity to Atg2 at the C terminus. This region also contains the conserved domain of unknown function DUF1162. Of interest, the expression of the TipC C-terminal coding sequence containing these 2 motifs largely complemented the mutant phenotype. Dictyostelium cells lacking TipC displayed a reduced number of autophagosomes visualized with the markers GFP-Atg18 and GFP-Atg8 and an impaired autophagic degradation as determined by a proteolytic cleavage assay. Downregulation of human VPS13A in HeLa cells by RNA interference confirmed the participation of the human protein in autophagy. VPS13A-depleted cells showed accumulation of autophagic markers and impaired autophagic flux.

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VPS13Regulates Membrane Morphogenesis During Sporulation inSaccharomyces cerevisiae

Cited by 101 publications

References 57 publications

Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells

Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells

Cohen Syndrome-associated Protein COH1 Physically and Functionally Interacts with the Small GTPase RAB6 at the Golgi Complex and Directs Neurite Outgrowth

TipC and the chorea-acanthocytosis protein VPS13A regulate autophagy inDictyosteliumand human HeLa cells

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