SAC1 lipid phosphatase and growth control of the secretory pathway

Blagoveshchenskaya, Anastasia; Mayinger, Peter

doi:10.1039/b810979f

Cited by 31 publications

(39 citation statements)

References 96 publications

(139 reference statements)

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“…Indeed, Sac3 belongs to the group of relatively non-specific evolutionarily conserved Sac1 homology-containing inositol polyphosphate phosphatases (Fig. 7.2) able to hydrolyze phosphate from any of the D-3, -4 or -5 positions in inositol in in vitro assays (Hughes et al 2000;Blagoveshchenskaya and Mayinger 2009;Majerus and York 2009). Although recombinant Fig4, the yeast Sac3 ortholog, hydrolyzes exclusively the D-5 phosphate in PtdIns(3,5)P 2 (Rudge et al 2004), such specificity is not reproduced with human and rat Sac3 proteins Yuan et al 2007).…”

Section: Arpikfyve and Sac3: The Pas Regulatory Triomentioning

confidence: 99%

PIKfyve and its Lipid Products in Health and in Sickness

Shisheva

2012

Current Topics in Microbiology and Immunology

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PIKfyve, a phosphoinositide 5-kinase synthesizing PtdIns(3,5)P₂ and PtdIns5P in a cellular context, belongs to an evolutionarily ancient gene family of PtdIns(3,5)P₂-synthesizing enzymes that, except for plants, are products of a single-copy gene across species. In the dozen years after its discovery, enormous progress has been made in characterizing the numerous PIKfyve cellular functions and the regulatory mechanisms that govern these functions. It became clear that PIKfyve does not act alone but, rather, it engages the scaffolding regulator ArPIKfyve and the phosphatase Sac3 to make a multiprotein "PAS" complex, so called for the first letters of the protein names. This complex relays antagonistic signals, one for synthesis, another for turnover of PtdIns(3,5)P₂, whose dysregulated coordination is linked to several human diseases. The physiological significance for each protein in the PAS complex is underscored by the early lethality of the mouse models with disruption in any of the three genes. This chapter summarizes our current knowledge of the diverse and complex functionality of PIKfyve and PtdIns(3,5)P₂/PtdIns5P products with particular highlights on recent discoveries of inherited or somatic mutations in PIKfyve and Sac3 linked to human disorders.

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Section: Arpikfyve and Sac3: The Pas Regulatory Triomentioning

confidence: 99%

PIKfyve and its Lipid Products in Health and in Sickness

Shisheva

2012

Current Topics in Microbiology and Immunology

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“…In S. cerevisiae, Sac1 is required for a variety of cell processes, including organization of actin cytoskeleton, secretory traffic, lipid metabolism and ER ATP transport (Blagoveshchenskaya and Mayinger, 2009;Foti et al, 2001). In this study, we identified homologous Sac1 in the dimorphic fungus, C. albicans, and characterized its functions in morphogenesis, cell wall integrity (CWI) and pathogenicity.…”

Section: Discussionmentioning

confidence: 98%

“…Further studies demonstrated that this protein participates in many cellular processes, such as organization of the actin cytoskeleton, secretory pathway, vacuolar function, ER function and sphingolipid metabolism (Blagoveshchenskaya and Mayinger, 2009;Foti et al, 2001). Deletion of ScSAC1 also results in inositol auxotrophy (Whitters et al, 1993), implying an essential role in inositol metabolism.…”

Section: Introductionmentioning

confidence: 97%

The actin-related protein Sac1 is required for morphogenesis and cell wall integrity in Candida albicans

Zhang

Jia

et al. 2015

Fungal Genetics and Biology

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“…It has been reported previously that SAC1 is localized to the Golgi membranes only when cells are starved for nutrients or growth factors, but remains in the ER under normal growth conditions (23,24). Given the role for PI(4)P in vesicle traffic from the trans Golgi network, starvation conditions that lodge SAC1 and thus deplete the local supply of PI(4)P in the Golgi may suppress anterograde traffic in cells that must cease net cell growth.…”

Section: Significancementioning

confidence: 95%

Phosphoregulatory protein 14-3-3 facilitates SAC1 transport from the endoplasmic reticulum

Pahuja

Wang

Blagoveshchenskaya

et al. 2015

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

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Most secretory cargo proteins in eukaryotes are synthesized in the endoplasmic reticulum and actively exported in membrane-bound vesicles that are formed by the cytosolic coat protein complex II (COPII). COPII proteins are assisted by a variety of cargo-specific adaptor proteins required for the concentration and export of secretory proteins from the endoplasmic reticulum (ER). Adaptor proteins are key regulators of cargo export, and defects in their function may result in disease phenotypes in mammals. Here we report the role of 14-3-3 proteins as a cytosolic adaptor in mediating SAC1 transport in COPII-coated vesicles. Sac1 is a phosphatidyl inositol-4 phosphate (PI4P) lipid phosphatase that undergoes serum dependent translocation between the endoplasmic reticulum and Golgi complex and controls cellular PI4P lipid levels. We developed a cell-free COPII vesicle budding reaction to examine SAC1 exit from the ER that requires COPII and at least one additional cytosolic factor, the 14-3-3 protein. Recombinant 14-3-3 protein stimulates the packaging of SAC1 into COPII vesicles and the sorting subunit of COPII, Sec24, interacts with 14-3-3. We identified a minimal sorting motif of SAC1 that is important for 14-3-3 binding and which controls SAC1 export from the ER. This LS motif is part of a 7-aa stretch, RLSNTSP, which is similar to the consensus 14-3-3 binding sequence. Homology models, based on the SAC1 structure from yeast, predict this region to be in the exposed exterior of the protein. Our data suggest a model in which the 14-3-3 protein mediates SAC1 traffic from the ER through direct interaction with a sorting signal and COPII.

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SAC1 lipid phosphatase and growth control of the secretory pathway

Cited by 31 publications

References 96 publications

PIKfyve and its Lipid Products in Health and in Sickness

PIKfyve and its Lipid Products in Health and in Sickness

The actin-related protein Sac1 is required for morphogenesis and cell wall integrity in Candida albicans

Phosphoregulatory protein 14-3-3 facilitates SAC1 transport from the endoplasmic reticulum

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