Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase

Wood, Christopher S.; Hung, Chih Ming; Huoh, Yu-San; Mousley, Carl J.; Stefan, Christopher J.; Bankaitis, Vytas A.; Ferguson, Kathryn M.; Burd, Christopher G.

doi:10.1091/mbc.e12-01-0077

Cited by 55 publications

(87 citation statements)

References 43 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A Golgi PI(4)P effector, GOLPH3, is involved in Golgi-plasma membrane transport and in the glycosylation of proteins (8,34,35). In yeast, Vps74, the ortholog of human GOLPH3, binds directly to Sac1 (36). We found that expression of GOLPH3 wt, but not GOLPH3 R90L, resulted in an increase in PI(4)P levels in the Golgi apparatus.…”

Section: Discussionmentioning

confidence: 76%

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

et al. 2014

View full text Add to dashboard Cite

Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIb, which generates PI(4)P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus. Cancer Res; 74(11); 3054-66. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 76%

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Sul2 (a sulfur permease), two plasma membrane-associated t-SNAREs (Sso1 and Sso2), and Rvs161, a lipid raft protein, were also isolated, consistent with the role of Rsp5 in membrane protein trafficking. Other membrane-associated interacting proteins included Vti1 and Sac1, which are Golgi membrane proteins, and Pil1, which is localized to the mitochondrial membrane [77][78][79].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin‐Activated Interaction Traps ( UBAIT s) identify E3 ligase binding partners

et al. 2015

View full text Add to dashboard Cite

We describe a new class of reagents for identifying substrates, adaptors, and regulators of HECT and RING E3s. UBAITs (UbiquitinActivated Interaction Traps) are E3-ubiquitin fusion proteins and, in an E1-and E2-dependent manner, the C-terminal ubiquitin moiety forms an amide linkage to proteins that interact with the E3, enabling covalent co-purification of the E3 with partner proteins. We designed UBAITs for both HECT (Rsp5, Itch) and RING (Psh1, RNF126, RNF168) E3s. For HECT E3s, trapping of interacting proteins occurred in vitro either through an E3 thioester-linked lariat intermediate or through an E2 thioester intermediate, and both WT and active-site mutant UBAITs trapped known interacting proteins in yeast and human cells. Yeast Psh1 and human RNF126 and RNF168 UBAITs also trapped known interacting proteins when expressed in cells. Human RNF168 is a key mediator of ubiquitin signaling that promotes DNA double-strand break repair. Using the RNF168 UBAIT, we identify H2AZ-a histone protein involved in DNA repair-as a new target of this E3 ligase. These results demonstrate that UBAITs represent powerful tools for profiling a wide range of ubiquitin ligases.

show abstract

“…The reduction in negative charge of the cis-and medial-Golgi relative to the TGN and late Golgi is the result of two factors. First, the negatively charged PtdIns(4)P is concentrated in the later Golgi because of the constant cycling of the PtdIns(4)P phosphatase Sac1 between the cis-Golgi and ER (33,34). Second, phosphatidylserine, another major negatively charged phospholipid, is located mostly in the inner leaflet of the ER and cis-Golgi membranes but in the outer leaflet of compartment membranes later in the secretory pathway (35).…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the binding of tryptophan-based motifs by δ-COP

Suckling

Poon

Travis

et al. 2015

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

View full text Add to dashboard Cite

Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding βγδζ-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding αβ'e-COP B-subcomplex. We present the structure of the C-terminal μ-homology domain of the yeast δ-COP subunit in complex with the WxW motif from its binding partner, the endoplasmic reticulum-localized Dsl1 tether. The motif binds at a site distinct from that used by the homologous AP μ subunits to bind YxxΦ cargo motifs with its two tryptophan residues sitting in compatible pockets. We also show that the Saccharomyces cerevisiae Arf GTPase-activating protein (GAP) homolog Gcs1p uses a related WxxF motif at its extreme C terminus to bind to δ-COP at the same site in the same way. Mutations designed on the basis of the structure in conjunction with isothermal titration calorimetry confirm the mode of binding and show that mammalian δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that δ-COP subunits bind Wx n(1-6) [WF] motifs within unstructured regions of proteins that influence the lifecycle of COPI-coated vesicles; this conclusion is supported by the observation that, in the context of a sensitizing domain deletion in Dsl1p, mutating the tryptophan-based motif-binding site in yeast causes defects in both growth and carboxypeptidase Y trafficking/processing. C OPI vesicles mediate retrograde trafficking from the Golgi to the endoplasmic reticulum (ER) and within the Golgi (reviewed in refs. 1-3). The COPI vesicle coat consists of two major components, coatomer and the small GTPase ADP ribosylation factor 1 (Arf1). Coatomer is an ∼600 kDa heteroheptameric complex consisting of two linked subcomplexes, the βγδζ-COP F-subcomplex and the αβ'e-COP B-subcomplex, all conserved from yeast to humans.Recent studies have led to a model for COPI-coated vesicle formation in which the F-subcomplex functions as a traditional Arf1:GTP effector but with two membrane-attached Arf1:GTP molecules binding to quasi-equivalent sites on a single F-subcomplex, recruiting F-subcomplex and its associated B-subcomplex onto the membrane en bloc (4). Once the vesicle has budded from its donor membrane, an Arf GTPase-activating protein (ArfGAP) catalyzes the hydrolysis of GTP on Arf1, and the Arf1:GDP dissociates from the membrane, followed later by the dissociation of the coatomer complex that was bound to the transport vesicle (5). ArfGAPs also have been proposed to function at different stages in vesicle biogenesis, both as terminators and, during an earlier cargoediting step, as effectors (reviewed in depth in ref. 6). In the final stages of its life, a COPI-coated vesicle docks with the ER via the Dsl1-tethering complex, completes uncoating, and finally undergoes SNARE-mediated fusion with the ER (7-9).The two main ArfGAPs associated with COPI-dependent retrograde transport in yeast are Gcs1p and Glo3p. These proteins can substitute for one another, at least partially,...

show abstract

Local control of phosphatidylinositol 4-phosphate signaling in the Golgi apparatus by Vps74 and Sac1 phosphoinositide phosphatase

Abstract: Signaling by phosphatidylinositol 4-kinases (PI4Ks) in the Golgi apparatus controls lipid homeostasis and protein-sorting pathways. Signaling is shown to be terminated on the medial cisterna by a complex of a PI4K effector, Vps74, and Sac1, the major PtdIns4P phosphatase in the cell.

Cited by 55 publications

References 43 publications

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

Ubiquitin‐Activated Interaction Traps ( UBAIT s) identify E3 ligase binding partners

Structural basis for the binding of tryptophan-based motifs by δ-COP

Contact Info

Product

Resources

About