A Role of Rab29 in the Integrity of the Trans-Golgi Network and Retrograde Trafficking of Mannose-6-Phosphate Receptor

Rab29 (also referred as Rab7L1) is a novel Rab protein, and is recently demonstrated to regulate phagocytosis and traffic from the Golgi to the lysosome. However, its roles in membrane trafficking have not been investigated extensively. Our results in this study revealed that Rab29 is associated with the trans-Golgi network (TGN), and is essential for maintaining the integrity of the TGN, because inhibition of the activity of Rab29 or depletion of Rab29 resulted in fragmentation of the TGN marked by TGN46. Expression of the dominant negative form Rab29T21N or shRNA-Rab29 also altered the distribution of mannose-6-phosphate receptor (M6PR), and interrupted the retrograde trafficking of M6PR through monitoring the endocytosis of CD8-tagged calcium dependent M6PR (cdM6PR) or calcium independent M6PR (ciM6PR), but without significant effects on the anterograde trafficking of vesicular stomatitis virus G protein (VSV-G). Our results suggest that Rab29 is essential for the integrity of the TGN and participates in the retrograde trafficking of M6PRs.

• Publication year

  2014

• Venue

  PLoS ONE

• Publication date

  2014-05-02

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1371/journal.pone.0096242PMID 24788816PMCID 4008501
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Rab GTPase regulation of membrane identity.

  2013cited by this paper
• A Role for Cargo in Arf-dependent Adaptor Recruitment*

  2013cited by this paper
• RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk.

  2013cited by this paper
• Retromer Guides STxB and CD8‐M6PR from Early to Recycling Endosomes, EHD1 Guides STxB from Recycling Endosome to Golgi

  2012cited by this paper
• Clarifying lysosomal storage diseases.

  2011cited by this paper
• Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella

  2011cited by this paper
• GCC185 plays independent roles in Golgi structure maintenance and AP-1–mediated vesicle tethering

  2011cited by this paper
• Rab36 regulates the spatial distribution of late endosomes and lysosomes through a similar mechanism to Rab34

  2010cited by this paper
• Rab7b controls trafficking from endosomes to the TGN

  2010cited by this paper
• Transport of mannose-6-phosphate receptors from the trans-Golgi network to endosomes requires Rab31.

  2009cited by this paper
• Sorting of lysosomal proteins.

  2009cited by this paper
• Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi.

  2009cited by this paper
• Interaction of Rab31 and OCRL‐1 in oligodendrocytes: Its role in transport of mannose 6‐phosphate receptors

  2009cited by this paper
• Multiple routes of protein transport from endosomes to the trans Golgi network

  2009cited by this paper
• Tracing the retrograde route in protein trafficking.

  2008cited by this paper
• Rab cascades and tethering factors in the endomembrane system

  2007cited by this paper
• Rab22B's role in trans-Golgi network membrane dynamics.

  2007cited by this paper
• The golgin GCC88 is required for efficient retrograde transport of cargo from the early endosomes to the trans-Golgi network.

  2007cited by this paper
• Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes

  2006cited by this paper
• Retrograde transport from endosomes to the trans-Golgi network

  2006cited by this paper
• TIP47 is a key effector for Rab9 localization

  2006cited by this paper
• A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling.

  2006cited by this paper
• Assay and functional properties of Rab34 interaction with RILP in lysosome morphogenesis.

  2005cited by this paper
• FAPP2 is involved in the transport of apical cargo in polarized MDCK cells

  2005cited by this paper
• Molecular basis for Golgi maintenance and biogenesis.

  2004influential reference
• Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer

  2004cited by this paper
• Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor

  2004cited by this paper
• Role of rab proteins in epithelial membrane traffic.

  2003cited by this paper
• Changing directions: clathrin-mediated transport between the Golgi and endosomes

  2003cited by this paper
• Cooperation of GGAs and AP-1 in Packaging MPRs at the Trans-Golgi Network

  2002cited by this paper
• Interorganellar regulation of lysosome positioning by the Golgi apparatus through Rab34 interaction with Rab-interacting lysosomal protein.

  2002cited by this paper
• Ykt6 Forms a SNARE Complex with Syntaxin 5, GS28, and Bet1 and Participates in a Late Stage in Endoplasmic Reticulum-Golgi Transport*

  2001cited by this paper
• Unravelling Golgi membrane traffic with green fluorescent protein chimeras.

  1998cited by this paper
• TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking.

  1998cited by this paper
• Protein transport from the secretory to the endocytic pathway in mammalian cells.

  1998cited by this paper
• Lysosomal storage diseases.

  1995cited by this paper
• Lysosomal storage diseases.

  1986cited by this paper

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  2020influential citation
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
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  2017cites this paper
• LRRK2 and Parkinson's Disease: From Lack of Structure to Gain of Function.

  2017cites this paper
• Rab29 activation of the Parkinson's disease‐associated LRRK2 kinase

  2017cites this paper
• Golgi trafficking defects in postnatal microcephaly: The evidence for “Golgipathies”

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
• Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease

  2015cites this paper
• Alterations in late endocytic trafficking related to the pathobiology of LRRK2-linked Parkinson's disease.

  2015cites this paper
• The GOLPH3 pathway regulates Golgi shape and function and is activated by DNA damage

  2015cites this paper
• Endocytic membrane trafficking and neurodegenerative disease

  2015cites this paper
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