Free oligosaccharides in the cytosol of Caenorhabditis elegans are generated through endoplasmic reticulum-Golgi trafficking

Toshihiko Kato, Kumiko Kitamura, Megumi Maeda, Yoshinobu Kimura, Takane Katayama, Hisashi Ashida, Kenji Yamamoto

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Free oligosaccharides (FOSs) in the cytosol of eukaryotic cells are mainly generated during endoplasmic reticulum (ER)-associated degradation (ERAD) of misfolded glycoproteins. We analyzed FOS of the nematode Caenorhabditis elegans to elucidate its detailed degradation pathway. The major FOSs were high mannose-type ones bearing 3-9 Manresidues. About 94% of the total FOSs had one GlcNAc at their reducing end (FOS-GN1), and the remaining 6% had two GlcNAc (FOS-GN2). A cytosolic endo-β-N-acetylglucosaminidase mutant (tm1208) accumulated FOS-GN2, indicating involvement of the enzyme in conversion of FOS-GN2 into FOS-GN1. The most abundant FOS in the wild type was Man 5GlcNAc1, the M5A′ isomer (Manα1- 3(Manα1-6)Manα1-6(Manα1-3)Manβ1-4GlcNAc), which is different from the corresponding M5B′ (Manα1-2Manα1- 2Manα1-3(Manα1-6)Manβ1-4GlcNAc) in mammals. Analyses of FOS in worms treated with Golgi α-mannosidase I inhibitors revealed decreases in Man5GlcNAc1 and increases in Man7GlcNAc 1. These results suggested that Golgi α-mannosidase I-like enzyme is involved in the production of Man5-6-GlcNAc1, which is unlike in mammals, in which cytosolic α-mannosidase is involved. Thus, we assumed that major FOSs in C. elegans were generated through Golgi trafficking. Analysis of FOSs from a Golgi α-mannosidase II mutant (tm1078) supported this idea, because GlcNAc1Man 5GlcNAc1, which is formed by the Golgi-resident GlcNAc-transferase I, was found as a FOS in the mutant. We concluded that significant amounts of misfolded glycoproteins in C. elegans are trafficked to the Golgi and are directly or indirectly retro-translocated into the cytosol to be degraded.

Original languageEnglish
Pages (from-to)22080-22088
Number of pages9
JournalJournal of Biological Chemistry
Issue number30
Publication statusPublished - Jul 27 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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