Rho GTPases orient directional sensing in chemotaxis

Wang, Yu; Senoo, Hiroshi; Sesaki, Hiromi; Iijima, Miho

doi:10.1073/pnas.1312540110

Cited by 40 publications

(66 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7A) (24,25). Whole-cell lysates of Dictyostelium cells expressing GFP fused to PTEN, PTEN A4 , and ePTEN were incubated with nitrocellulose membranes carrying different phospholipids and their interactions were detected using anti-GFP antibodies.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities

Nguyen¹,

Yang²,

Afkari³

et al. 2014

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

Self Cite

View full text Add to dashboard Cite

The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate (PIP3) is a key regulator of cell proliferation, survival, and migration and the enzyme that dephosphorylates it, phosphatase and tensin homolog (PTEN), is an important tumor suppressor. As excess PIP3 signaling is a hallmark of many cancers, its suppression through activation of PTEN is a potential cancer intervention. Using a heterologous expression system in which human PTEN-GFP is expressed in Dictyostelium cells, we identified mutations in the membrane-binding regulatory interface that increase the recruitment of PTEN to the plasma membrane due to enhanced association with PI(4,5)P2. We engineered these into an enhanced PTEN (ePTEN) with approximately eightfold increased ability to suppress PIP3 signaling. Upon expression in human cells, ePTEN decreases PIP3 levels in the plasma membrane; phosphorylation of AKT, a major downstream event in PIP3 signaling; and cell proliferation and migration. Thus, the activation of PTEN can readjust PIP3 signaling and may serve as a feasible target for anticancer therapies.protein engineering | PI3 kinase signaling | membrane localization | chemotaxis | protein interaction

show abstract

Section: Resultsmentioning

confidence: 99%

“…The lipid dot blot assay was performed as described previously (24,25,36). Briefly, Dictyostelium cells expressing different PTEN-GFP constructs were starved for 2 h in 10 mM phosphate buffer (pH 7.0), 2 mM MgSO 4 , and 0.2 mM CaCl 2 and then washed twice in 20 mL of ice-cold 10 mM sodium phosphate (pH 7.0).…”

Section: Methodsmentioning

confidence: 99%

Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities

Nguyen¹,

Yang²,

Afkari³

et al. 2014

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…GxcU is one of four D. discoideum proteins (GxcU, GxcV, GxcW and GxcX) with a domain structure similar to that of Frabin 35 : a Dbl-Rho family GEF domain, followed by a PH domain and a FYVE domain. GxcU is largely unstudied, but knockout strains show that this gene is not essential for life 36 . Frabin ( F GD1-related F- a ctin bin ding protein) is one of 7 closely related so-called FGD (faciogenital dysplasia) proteins, FGD1-6 and FRG ( F GD1-related Cdc42- G EF)/FARP2, thought to function as Cdc42 GEFs.…”

Section: Resultsmentioning

confidence: 99%

Lowe Syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL inDictyostelium discoideum

Lüscher

FroÌˆhlich

Barisch

et al. 2019

Preprint

View full text Add to dashboard Cite

SummaryMutations of the inositol 5-phosphatase OCRL cause Lowe Syndrome (LS), characterized by congenital cataract, low IQ and defective kidney proximal tubule resorption. A key subset of LS mutants abolishes OCRL’s interactions with endocytic adaptors containing F&H peptide motifs. Converging unbiased methods examining human peptides and the unicellular phagocytic organism Dictyostelium discoideum, reveal that, like OCRL, the Dictyostelium OCRL orthologue Dd5P4 binds two proteins closely related to the F&H proteins APPL1 and Ses1/2 (also referred to as IPIP27A/B). In addition, a novel conserved F&H interactor was identified, GxcU (in Dictyostelium) and the Cdc42-GEF Frabin (in human cells). Examining these proteins in Dictyostelium discoideum, we find that, like OCRL, Dd5P4 acts at well-conserved and physically distinct endocytic stations. Dd5P4 functions in coordination with F&H proteins to control membrane deformation at multiple stages of endocytosis, and suppresses GxcU-mediated activity during fluid-phase micropinocytosis. We also reveal that OCRL/Dd5P4 acts at the contractile vacuole, an exocytic osmoregulatory organelle. We propose F&H peptide-containing proteins may be key modifiers of LS phenotypes.

show abstract

“…The multiple genes in the Rac/Rho family, and their multiple GEFs and GAPs make genetic dissection of their functions difficult. However, single knock-out mutants of RacC and RacE and the GEF GxcT have severe growth defects in liquid medium, but whether this is due to a macropinocytosis defect is not known (Wang et al, 2013).…”

Section: Downstream Of Pip3: Akt and Sgk Protein Kinasesmentioning

confidence: 99%

Living on soup: macropinocytic feeding in amoebae

Kay¹,

Williams²,

Manton³

et al. 2019

Int. J. Dev. Biol.

View full text Add to dashboard Cite

Macropinocytosis is used by a variety of amoebae for feeding on liquid medium. The amoebae project cups and ruffles from their plasma membrane, driven by actin polymerization, and eventually fuse these back to the membrane, entrapping droplets of medium into internal vesicles. These vesicles are of up to several microns in diameter and are processed through the lysosomal digestive system to extract nutrients. Recognizably the same process is used in metazoan cells for a number of medically important purposes, including the pathological growth of cancer cells. We describe the discovery of macropinocytosis in Dictyostelium amoebae, its genetic regulation by the NF1 RasGAP, and the tools available for its investigation. Work on Dictyostelium over the last 30 years has identified many genes that may be important for macropinocytosis, which are listed at dictyBase, and give a basis for mechanistic studies. We argue that the actin cytoskeleton is organized for macropinocytosis by a signalling patch of PIP3 and active Ras and Rac, together with their regulatory proteins and effectors, including the protein kinases Akt and SGK. The Scar/ WAVE complex is recruited to the periphery of this patch, triggering the formation of a hollow ring of protrusive actin polymerization, and eventually a macropinocytic cup. Major problems to be addressed include: the dynamics sustaining macropinocytic patches and the mechanism of Scar/WAVE recruitment; the mechanisms of cup closure and of membrane fusion; the ecological situations where amoebae feed by macropinocytosis; and the evolutionary relationship between macropinocytosis and growth factor signalling.

show abstract

Rho GTPases orient directional sensing in chemotaxis

Cited by 40 publications

References 59 publications

Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities

Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities

Lowe Syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL inDictyostelium discoideum

Living on soup: macropinocytic feeding in amoebae

Contact Info

Product

Resources

About