Inhibition of Calcium-independent Mannose 6-Phosphate Receptor Incorporation into trans-Golgi Network-derived Clathrin-coated Vesicles by Wortmannin

Gaffet, Patrick; Jones, Arwyn Tomos; Clague, Michael J.

doi:10.1074/jbc.272.39.24170

Cited by 33 publications

(21 citation statements)

References 37 publications

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“…Wortmannin inhibited the delivery of cathepsin D to lysosomes (28,72) apparently through an effect on the sorting of cargo into vesicles rather than through an inhibition of vesicle budding. Wortmannin had only a minor effect on the production of small vesicles from trans-Golgi network (TGN) membranes but prevented the mannose 6-phosphate receptor from entering into vesicles (110). However, yeast Vps34p or mammalian PtdIns3K have not been shown to be located on Golgi or TGN membranes.…”

Section: Ptdins3k and Vps34pmentioning

confidence: 99%

“…PtdIns3K inhibitors were found to disrupt the sorting of lysosomal proteins in the Golgi, and this was interpreted to mean that the site of PtdIns3K action was the TGN (31,72). A PtdIns3K activity was found to be required for budding of vesicles containing the polyimmunoglobulin receptor from isolated rat hepatocyte Golgi membranes (169), and wortmannin was observed to inhibit the sorting of mannose 6-phosphate receptors (M6PRs) into vesicles, but not the budding of vesicles, from the TGN (110). Wortmannin treatment also altered the morphology of the TGN (139).…”

Section: Ptdins(3)p On the Golgimentioning

confidence: 99%

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Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

263

267

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Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.

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Section: Ptdins3k and Vps34pmentioning

confidence: 99%

Section: Ptdins(3)p On the Golgimentioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

263

267

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“…By contrast, we observed a strong inhibition of the starvation-induced redistribution of mAtg9 with a PtdIns 3-kinase inhibitor. It has been shown that PtdIns 3-kinase is required for the exit of CI-MPR (Gaffet et al, 1997). Furthermore, it has been reported that there may be an inhibitor-sensitive endosomal trafficking step, involving CI-MPR, which is not mediated by type III PtdIns 3-kinase (Row et al, 2001).…”

Section: Localization and Topology Of Matg9mentioning

confidence: 99%

Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes

Young

Chan

et al. 2006

Journal of Cell Science

727

775

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Autophagy, fundamentally a lysosomal degradation pathway, functions in cells during normal growth and certain pathological conditions, including starvation, to maintain homeostasis. Autophagosomes are formed through a mechanism that is not well understood, despite the identification of many genes required for autophagy. We have studied the mammalian homologue of Atg9p, a multi-spanning transmembrane protein essential in yeast for autophagy, to gain a better understanding of the function of this ubiquitious protein. We show that both the N-and C-termini of mammalian Atg9 (mAtg9) are cytosolic, and predict that mAtg9 spans the membrane six times. We find that mAtg9 is located in the trans-Golgi network and late endosomes and colocalizes with TGN46, the cation-independent mannose-6-phosphate receptor, Rab7 and Rab9. Amino acid starvation or rapamycin treatment, which upregulates autophagy, causes a redistribution of mAtg9 from the TGN to peripheral, endosomal membranes, which are positive for the autophagosomal marker GFP-LC3. siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution. The redistribution of mAtg9 also requires PI 3-kinase activity, and is reversed after restoration of amino acids. We speculate that starvation-induced autophagy, which requires mAtg9, may rely on an alteration of the steadystate trafficking of mAtg9, in a Atg1-dependent manner.Supplementary material available online at

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“…Interestingly, vesicles from the TGN and plasma membrane may intersect at the endosomal-TGN network-the site of Nef/ MHC-I accumulation (14,22,33,44), and a known site of PACS-1 activity (29,48). PI 3-kinase, a regulator of TGN-toendosome/lysosome trafficking (3,8,11), is necessary for Nef's effects on MHC-I (44), providing additional evidence for the role of this pathway. The ability of Nef to affect the trafficking of MHC-I at both the TGN and the plasma membrane would maximize the effects of Nef on antigen presentation and escape of HIV-infected cells from CTL killing.…”

Section: Hiv-1 Nef Associates With Mhc-i In Vivomentioning

confidence: 99%