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Sorting of Mannose 6-Phosphate Receptors Mediated by the GGAs

Puertollano, Rosa, Aguilar, Rubén C., Gorshkova, Inna, Crouch, Robert J., Bonifacino, Juan S.·2001·Science
DOI 10.1126/science.1060750
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Abstract

The delivery of soluble hydrolases to lysosomes is mediated by the cation-independent and cation-dependent mannose 6-phosphate receptors. The cytosolic tails of both receptors contain acidic-cluster-dileucine signals that direct sorting from the trans-Golgi network to the endosomal-lysosomal system. We found that these signals bind to the VHS domain of the Golgi-localized, γ-ear–containing, ARF-binding proteins (GGAs). The receptors and the GGAs left the trans-Golgi network on the same tubulo-vesicular carriers. A dominant-negative GGA mutant blocked exit of the receptors from the trans-Golgi network. Thus, the GGAs appear to mediate sorting of the mannose 6-phosphate receptors at the trans-Golgi network.

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Crossref · 10.1126/science.1060750

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  • The GGA1 dominant-negative variant interferes with transport of cargo protein from TGN to endosomal/lysosomal compartments.

    “The GGA1 DN variant has been shown to interfere with transport of cargo protein from TGN to endosomal/lysosomal compartments (Puertollano et al., 2001).”

    From GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide (2006) · cites this paper as Puertollano et al., 2001

  • Expression of GGA1 DN inhibits the transport of specific cargo proteins (e.g., M6PRs) from the TGN to endosomal compartments.

    “GGA proteins could also facilitate transport of specific cargo proteins [e.g., the mannose 6 phosphate receptors (M6PRs)] from the TGN to endosomal compartments and the expression of GGA1 DN inhibits this transport route (Puertollano et al., 2001;Zhu et al., 2001).”

    From GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide (2006) · cites this paper as Puertollano et al., 2001

  • GGAs mediate forward trafficking of the M6PR from the TGN to endosomal compartments.

    “Indeed, GGAs also mediate forward trafficking of the M6PR from the TGN to endosomal compartments (Puertollano et al., 2001)”

    From GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide (2006) · cites this paper as Puertollano et al., 2001

  • GGA proteins facilitate transport of specific cargo proteins (e.g., M6PRs) from the TGN to endosomal compartments.

    “GGA proteins could also facilitate transport of specific cargo proteins [e.g., the mannose 6 phosphate receptors (M6PRs)] from the TGN to endosomal compartments and the expression of GGA1 DN inhibits this transport route (Puertollano et al., 2001;Zhu et al., 2001).”

    From GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide (2006) · cites this paper as Puertollano et al., 2001

Citations

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Research works printed but not linked: 19

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  19. We thank X. Zhu for technical assistance; J. Presley for help with fluorescence microscopy; L. Greene (APs) R. Lodge (CD-MPR-GFP) S. Kornfeld (rabbit anti–CD-MPR) and E. Rodrı́guez-Boulan (mouse anti–LAMP-1) for reagents; J. Lippincott-Schwartz C. Jackson C. Mullins. M. Boehm and S. Caplan for comments on the manuscript; and S. Kornfeld for sharing unpublished observations. R.P. was supported by the Fundación Ramón Areces.

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Metadata

Authors
Puertollano, R., Aguilar, R. C., Gorshkova, I., Crouch, R. J., & Bonifacino, J. S.
Affiliations
  • Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2001-06
Volume
292
Issue
5522
Pages
1712-1716
ISSN
  • 0036-8075
  • 1095-9203
DOI
10.1126/science.1060750
Cited by
345
References
0
Language
en

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