Rab GTPase regulation of retromer-mediated cargo export during endosome maturation

Liu, Ting Ting; Gomez, Timothy S.; Sackey, Bridget K.; Billadeau, Daniel D.; Burd, Christopher G.

doi:10.1091/mbc.e11-11-0915

Cited by 114 publications

(133 citation statements)

References 39 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…In further support of this model, we recently found that in yeast cells lacking Ypt7-GTP (the ortholog of RAB7), retromer cargo accumulates in the endosome (8) and, in cultured human cells, acquisition of RAB7 on the endosome by Rab conversion is temporally correlated with the appearance of retromer-coated tubules that bud from the endosome (33). The biochemical reconstitution system established here provides an avenue to definitively address these questions.…”

Section: Discussionsupporting

confidence: 57%

“…In yeast, the Vps5-Vps17 SNX-BAR heterodimer, which was originally defined as stoichiometric components of retromer, is required for retromer endosome localization, but Snx3 is not (8,12). The stable pentameric form of yeast SNX-BAR retromer, however, is distinguished from metazoan retromer, which does not associate avidly with SNX-BAR proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The region of VPS35 containing the SNX3 binding site lies immediately N-terminal to the Rab7 binding site (repeat 6) that we identified (8) and overlaps the minimal VPS26 binding region, raising the possibility that SNX3 may compete with VPS26 and/or RAB7 or, alternatively, that it forms a supercomplex with retromer and RAB7. To distinguish these possibilities, we immobilized GST-RAB7 fusion proteins on beads and incubated them with purified recombinant retromer, SNX3, or retromer and SNX3 together, and then determined which proteins were captured (Fig.…”

Section: Significancementioning

confidence: 95%

“…Retromer is an effector of RAB7A [henceforth referred to as RAB7 (human) or Ypt7 (yeast)], a GTPase regulator of endosome dynamics and depletion of RAB7-GTP in cells results in a substantial loss of endosome-associated retromer (4)(5)(6)(7)(8)(9). In addition to GTPase signaling modules, interactions of coat proteins with membrane lipids, such as phosphoinositides, contribute to coat assembly by increasing the avidity of membrane binding.…”

mentioning

confidence: 99%

See 3 more Smart Citations

A mechanism for retromer endosomal coat complex assembly with cargo

Harrison

Hung

Liu

et al. 2013

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

Self Cite

146

172

View full text Add to dashboard Cite

Retromer is an evolutionarily conserved protein complex composed of the VPS26, VPS29, and VPS35 proteins that selects and packages cargo proteins into transport carriers that export cargo from the endosome. The mechanisms by which retromer is recruited to the endosome and captures cargo are unknown. We show that membrane recruitment of retromer is mediated by bivalent recognition of an effector of PI3K, SNX3, and the RAB7A GTPase, by the VPS35 retromer subunit. These bivalent interactions prime retromer to capture integral membrane cargo, which enhances membrane association of retromer and initiates cargo sorting. The role of RAB7A is severely impaired by a mutation, K157N, that causes Charcot-Marie-Tooth neuropathy 2B. The results elucidate minimal requirements for retromer assembly on the endosome membrane and reveal how PI3K and RAB signaling are coupled to initiate retromer-mediated cargo export.sorting nexin | mass spectrometry | biochemical reconstitution | proteoliposome

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 95%

mentioning

confidence: 99%

See 2 more Smart Citations

A mechanism for retromer endosomal coat complex assembly with cargo

Harrison

Hung

Liu

et al. 2013

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

Self Cite

146

172

View full text Add to dashboard Cite

show abstract

“…First, overexpressed yeast Rab7 (Ypt7) causes a premature fusion with vacuoles and delivery of cargo receptors to the vacuole surface (Balderhaar et al , 2010 ). Second, mutants in retromer that bind efficiently to Rab7 interfere with vacuole morphology, likely due to a prolonged interaction of retromer with Rab7 (Liu et al , 2012 ). The Rab7 binding to two distinct machineries that need to be coordinated at the late endosome leaves the question on how Rab7 activation is coordinated.…”

Section: Even Though the Exact Organization Of Such Zonesmentioning

confidence: 99%

Cellular microcompartments constitute general suborganellar functional units in cells

Holthuis

Ungermann

2013

Biological Chemistry

View full text Add to dashboard Cite

All cells are compartmentalized to facilitate enzymatic reactions or cellular dynamics. In eukaryotic cells, organelles differ in their protein/lipid repertoire, luminal ion composition, pH, and redox status. In addition, organelles contain specialized subcompartments even within the same membrane or within its lumen. Moreover, the bacterial plasma membrane reveals a remarkable degree of organization, which is recapitulated in eukaryotic cells and often linked to cell signaling. Finally, protein-based compartments are also known in the bacterial and eukaryotic cytosol. As the organizing principle of such cellular subcompartments is likely similar, previous definitions like rafts, microdomains, and all kinds of ' -somes ' fall short as a general denominator to describe such suborganellar structures. Within this review, we will introduce the term cellular microcompartment as a general suborganellar functional unit and discuss its relevance to understand subcellular organization and function.

show abstract

TPI1‐reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis

Liu

Tey

Mao

et al. 2021

J of Extracellular Vesicle

View full text Add to dashboard Cite

Rab GTPases are major mediators that ensure the proper spatiotemporal regulation of intracellular trafficking. Functional impairment and altered expression of Rab proteins have been revealed in various human cancers. There is an emerging evidence about the role of Rab proteins in the biogenesis of extracellular vesicles (EVs). In hepatocellular carcinoma (HCC), using RNA sequencing comparing expression profiles of adjacent non‐tumorous tissues and HCC, Rab20 is identified to be the most frequently downregulated Rab member in HCC. Functionally, restoration of Rab20 in metastatic HCC cells results in the release of EVs with a diminished activity to promote cell growth, motility and metastasis. Conversely, EVs released from normal liver cells with Rab20 knockdown loses suppressive effect on HCC cell growth and motility. Proteomic profiling revealed the level of triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, in EVs to be positively associated with Rab20 expression of the releasing cells. TPI1 targeted to be expressed in EVs released by Rab20 knockdown cells compromises the oncogenic activity of EVs. Besides, EVs released by TPI1 knockdown cells recapitulates the promoting effect of EVs derived from HCC cells with Rab20 underexpression. Aerobic glycolysis is beneficial to the survival and proliferation of tumour cells. Here, we observed that the enhanced cell growth and motility are driven by the enhanced aerobic glycolysis induced by EVs with reduced TPI1. The addition of glycolytic inhibitor blocks the promoting effect of EVs with reduced TPI1. Taken together, our study provides a mechanistic link among tumour cell‐derived EVs and glucose metabolism in HCC with Rab20 deregulation.

show abstract

Rab GTPase regulation of retromer-mediated cargo export during endosome maturation

Cited by 114 publications

References 39 publications

A mechanism for retromer endosomal coat complex assembly with cargo

A mechanism for retromer endosomal coat complex assembly with cargo

Cellular microcompartments constitute general suborganellar functional units in cells

TPI1‐reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis

Contact Info

Product

Resources

About