GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain

Hung Hsiang Huang, Antti Hassinen, Subha Sundaram, Andrej Nikolai Spiess, Sakari Kellokumpu, Pamela Stanley

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Abstract

Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP-L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis.

Original languageEnglish (US)
Article numbere08916
JournaleLife
Volume4
Issue numberSeptember2015
DOIs
StatePublished - Sep 15 2015

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Huang, H. H., Hassinen, A., Sundaram, S., Spiess, A. N., Kellokumpu, S., & Stanley, P. (2015). GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain. eLife, 4(September2015), [e08916]. https://doi.org/10.7554/eLife.08916