Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport

Tetsuya Hirata, Morihisa Fujita, Shota Nakamura, Kazuyoshi Gotoh, Daisuke Motooka, Yoshiko Murakami, Yusuke Maeda, Taroh Kinoshita

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33 Citations (Scopus)

Abstract

The importance of endosome-to-trans-Golgi network (TGN) retrograde transport in the anterograde transport of proteins is unclear. In this study, genome-wide screening of the factors necessary for efficient anterograde protein transport in human haploid cells identified subunits of the Golgi-associated retrograde protein (GARP) complex, a tethering factor involved in endosome-to-TGN transport. Knockout (KO) of each of the four GARP subunits, VPS51-VPS54, in HEK293 cells caused severely defective anterograde transport of both glycosylphosphatidylinositol (GPI)-anchored and transmembrane proteins from the TGN. Overexpression of VAMP4, v-SNARE, in VPS54-KO cells partially restored not only endosome-to-TGN retrograde transport, but also anterograde transport of both GPI-anchored and transmembrane proteins. Further screening for genes whose overexpression normalized the VPS54-KO phenotype identified TMEM87A, encoding an uncharacterized Golgi-resident membrane protein. Overexpression of TMEM87A or its close homologue TMEM87B in VPS54-KO cells partially restored endosome-to-TGN retrograde transport and anterograde transport. Therefore GARP-and VAMP4-dependent endosome-to-TGN retrograde transport is required for recycling of molecules critical for efficient post-Golgi anterograde transport of cell-surface integral membrane proteins. In addition, TMEM87A and TMEM87B are involved in endosome-to-TGN retrograde transport.

Original languageEnglish
Pages (from-to)3071-3084
Number of pages14
JournalMolecular Biology of the Cell
Volume26
Issue number17
DOIs
Publication statusPublished - Sep 1 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Hirata, T., Fujita, M., Nakamura, S., Gotoh, K., Motooka, D., Murakami, Y., Maeda, Y., & Kinoshita, T. (2015). Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport. Molecular Biology of the Cell, 26(17), 3071-3084. https://doi.org/10.1091/mbc.E14-11-1568