Vac14 Protein Multimerization Is a Prerequisite Step for Fab1 Protein Complex Assembly and Function

Alghamdi, Tamadher A.; Ho, Cheuk Y.; Mrakovic, Amra; Taylor, Danielle; Mao, Daniel Y.L.; Botelho, Roberto J.

doi:10.1074/jbc.m113.453712

Cited by 28 publications

(28 citation statements)

References 35 publications

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“…8A,B). This vacuolar dot has previously been observed for Atg18-GFP (Strømhaug et al, 2004) and Fig4-GFP (Rudge et al, 2004), the latter of which is known to be in a complex with Vac14p and Fab1p (Alghamdi et al, 2013). We show here that Atg18p, Vac14p and Fab1p are also localized within this vacuolar dot and colocalize with Sna4-dsRed.…”

Section: Pmp3p Binds To Phosphorylated Phosphoinositides Phosphatidisupporting

confidence: 52%

The yeast Pmp3p has a significant role in plasma membrane organization

Block

Szopinska

Guerriat

et al. 2015

Journal of Cell Science

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Pmp3p-related proteins are highly conserved proteins that exist in bacteria, yeast, nematodes and plants, and its transcript is regulated in response to abiotic stresses, such as low temperature or high salinity. Pmp3p was originally identified in Saccharomyces cerevisiae, and it belongs to the sensitive to Na + (SNA)-protein family, which comprises four members -Pmp3p/Sna1p, Sna2p, Sna3p and Sna4p. Deletion of the PMP3 gene conferred sensitivity to cytotoxic cations, whereas removal of the other SNA genes did not lead to clear phenotypic effects. It has long been believed that Pmp3p-related proteins have a common and important role in the modulation of plasma membrane potential and in the regulation of intracellular ion homeostasis. Here, we show that several growth phenotypes linked to PMP3 deletion can be modulated by the removal of specific genes involved in sphingolipid synthesis. These genetic interactions, together with lipid binding assays and epifluorescence microscopy, as well as other biochemical experiments, suggest that Pmp3p could be part of a phosphoinositide-regulated stress sensor.

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Section: Pmp3p Binds To Phosphorylated Phosphoinositides Phosphatidisupporting

confidence: 52%

The yeast Pmp3p has a significant role in plasma membrane organization

Block

Szopinska

Guerriat

et al. 2015

Journal of Cell Science

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“…In vac14⌬ cells, active Fab1 protein complexes fail to assemble, reducing PtdIns(3,5)P 2 levels to 10% of the wild type (27,28,45,46). In comparison, atg18⌬ cells exhibit a 5-10-fold increase in the levels of PtdIns(3,5)P 2 (47).…”

Section: Accumulation Of Quinacrine and Cdcfda In Yeast Vacuoles-mentioning

confidence: 99%

The Fab1/PIKfyve Phosphoinositide Phosphate Kinase Is Not Necessary to Maintain the pH of Lysosomes and of the Yeast Vacuole

Choy

Wattson

et al. 2015

Journal of Biological Chemistry

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Background: Based on qualitative pH probes, loss of Fab1/PIKfyve was thought to impair vacuolar/lysosomal acidification. Results: Using several quantitative assays, vacuoles/lysosomes remained acidic in Fab1/PIKfyve-inhibited cells in a V-ATPasedependent manner. Conclusion: Fab1/PIKfyve is not necessary to maintain the steady-state vacuolar/lysosomal pH. Significance: Contrary to current thought, we propose a model in which Fab1/PIKfyve is dispensable to maintain vacuolar/ lysosomal acidification.

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“…The carboxyterminal region is crucial for the interaction with FIG4 and also contains a PDZ-binding motif, which binds to nNOS (5,(7)(8)(9)(10)(11). Moreover, Vac14-oligomerization, which is essential for the nucleation of an active Vac14-complex, overlaps with the FIG4 interaction binding site (5,6,12,13).…”

mentioning

confidence: 99%

The Vac14-interaction Network Is Linked to Regulators of the Endolysosomal and Autophagic Pathway

Schulze

Vollenbröker

Braun

et al. 2014

Molecular & Cellular Proteomics

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The scaffold protein Vac14 acts in a complex with the lipid kinase PIKfyve and its counteracting phosphatase FIG4, regulating the interconversion of phosphatidylinositol-3-phosphate to phosphatidylinositol-3,5-bisphosphate. Dysfunctional Vac14 mutants, a deficiency of one of the Vac14 complex components, or inhibition of PIKfyve enzymatic activity results in the formation of large vacuoles in cells. How these vacuoles are generated and which processes are involved are only poorly understood. Here we show that ectopic overexpression of wild-type Vac14 as well as of the PIKfyve-binding deficient Vac14 L156R mutant causes vacuoles. Vac14-dependent vacuoles and PIKfyve inhibitor-dependent vacuoles resulted in elevated levels of late endosomal, lysosomal, and autophagy-associated proteins. However, only late endosomal marker proteins were bound to the membranes of these enlarged vacuoles. In order to decipher the linkage between the Vac14 complex and regulators of the endolysosomal pathway, a protein affinity approach combined with multidimensional protein identification technology was conducted, and novel molecular links were unraveled. We found and verified the interaction of Rab9 and the Rab7 GAP TBC1D15 with Vac14. The identified Rab-related interaction partners support the theory that the regulation of vesicular transport processes and phosphatidylinositolmodifying enzymes are tightly interconnected. Molecular

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Vac14 Protein Multimerization Is a Prerequisite Step for Fab1 Protein Complex Assembly and Function

Cited by 28 publications

References 35 publications

The yeast Pmp3p has a significant role in plasma membrane organization

The yeast Pmp3p has a significant role in plasma membrane organization

The Fab1/PIKfyve Phosphoinositide Phosphate Kinase Is Not Necessary to Maintain the pH of Lysosomes and of the Yeast Vacuole

The Vac14-interaction Network Is Linked to Regulators of the Endolysosomal and Autophagic Pathway

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