Spatial regulation of golgi phosphatidylinositol-4-phosphate is required for enzyme localization and glycosylation fidelity

Fei Ying Cheong, Vandana Sharma, Anastasia Blagoveshchenskaya, Viola M.J. Oorschot, Ben Brankatschk, Judith Klumperman, Hudson H. Freeze, Peter Mayinger

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The enrichment of phosphatidylinositol-4-phosphate (PI(4)P) at the trans Golgi network (TGN) is instrumental for proper protein and lipid sorting, yet how the restricted distribution of PI(4)P is achieved remains unknown. Here, we show that lipid phosphatase Suppressor of actin mutations 1 (SAC1) is crucial for the spatial regulation of Golgi PI(4)P. Ultrastructural analysis revealed that SAC1 is predominantly located at cisternal Golgi membranes but is absent from the TGN, thus confining PI(4)P to the TGN. RNAi-mediated knockdown of SAC1 caused changes in Golgi morphology and mislocalization of Golgi enzymes. Enzymes involved in glycan processing such as mannosidase-II (Man-II) and N-acetylglucosamine transferase-I (GnT-I) redistributed to aberrant intracellular structures and to the cell surface in SAC1 knockdown cells. SAC1 depletion also induced a unique pattern of Golgi-specific defects in N-and O-linked glycosylation. These results indicate that SAC1 organizes PI(4)P distribution between the Golgi complex and the TGN, which is instrumental for resident enzyme partitioning and Golgi morphology.

Original languageEnglish (US)
Pages (from-to)1180-1190
Number of pages11
JournalTraffic
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2010

Keywords

  • Glycosylation
  • Golgi apparatus
  • Phosphoinositides
  • SAC1
  • Secretory pathway

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Cheong, F. Y., Sharma, V., Blagoveshchenskaya, A., Oorschot, V. M. J., Brankatschk, B., Klumperman, J., Freeze, H. H., & Mayinger, P. (2010). Spatial regulation of golgi phosphatidylinositol-4-phosphate is required for enzyme localization and glycosylation fidelity. Traffic, 11(9), 1180-1190. https://doi.org/10.1111/j.1600-0854.2010.01092.x