trappc11 is required for protein glycosylation in zebrafish and humans

Mol Biol Cell. 2016 Apr 15;27(8):1220-34. doi: 10.1091/mbc.E15-08-0557. Epub 2016 Feb 24.


Activation of the unfolded protein response (UPR) can be either adaptive or pathological. We term the pathological UPR that causes fatty liver disease a "stressed UPR." Here we investigate the mechanism of stressed UPR activation in zebrafish bearing a mutation in thetrappc11gene, which encodes a component of the transport protein particle (TRAPP) complex.trappc11mutants are characterized by secretory pathway defects, reflecting disruption of the TRAPP complex. In addition, we uncover a defect in protein glycosylation intrappc11mutants that is associated with reduced levels of lipid-linked oligosaccharides (LLOs) and compensatory up-regulation of genes in the terpenoid biosynthetic pathway that produces the LLO anchor dolichol. Treating wild-type larvae with terpenoid or LLO synthesis inhibitors phenocopies the stressed UPR seen intrappc11mutants and is synthetically lethal withtrappc11mutation. We propose that reduced LLO level causing hypoglycosylation is a mechanism of stressed UPR induction intrappc11mutants. Of importance, in human cells, depletion of TRAPPC11, but not other TRAPP components, causes protein hypoglycosylation, and lipid droplets accumulate in fibroblasts from patients with theTRAPPC11mutation. These data point to a previously unanticipated and conserved role for TRAPPC11 in LLO biosynthesis and protein glycosylation in addition to its established function in vesicle trafficking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Atorvastatin / pharmacology
  • Dolichols / biosynthesis
  • Dolichols / genetics
  • Glycosylation
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism
  • Humans
  • Larva / drug effects
  • Larva / metabolism
  • Lipids / chemistry
  • Liver / metabolism
  • Liver / pathology
  • Mutation
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism*
  • Terpenes / metabolism
  • Terpenes / pharmacology
  • Unfolded Protein Response* / drug effects
  • Unfolded Protein Response* / genetics
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Dolichols
  • Lipids
  • Oligosaccharides
  • TRAPPC11 protein, human
  • TRAPPC11 protein, zebrafish
  • Terpenes
  • Vesicular Transport Proteins
  • Zebrafish Proteins
  • Atorvastatin