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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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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Endoplasmic Reticulum
Energy transfer
Polysaccharides
N-Acetylglucosaminyltransferases
Fluorescence Resonance Energy Transfer
Spermatocytes
Spermatids
Secretory Pathway
Energy Transfer
Spermatogenesis
Cultured Cells
Assays
Fluorescence
Cells
Membranes
invariant chain
N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase

ASJC Scopus subject areas

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

GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain. / Huang, Hung Hsiang; Hassinen, Antti; Sundaram, Subha; Spiess, Andrej Nikolai; Kellokumpu, Sakari; Stanley, Pamela.

In: eLife, Vol. 4, No. September2015, e08916, 15.09.2015.

Research output: Contribution to journalArticle

Huang, HH, Hassinen, A, Sundaram, S, Spiess, AN, Kellokumpu, S & Stanley, P 2015, 'GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain', eLife, vol. 4, no. September2015, e08916. https://doi.org/10.7554/eLife.08916
Huang HH, Hassinen A, Sundaram S, Spiess AN, Kellokumpu S, Stanley P. GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain. eLife. 2015 Sep 15;4(September2015). e08916. https://doi.org/10.7554/eLife.08916
Huang, Hung Hsiang ; Hassinen, Antti ; Sundaram, Subha ; Spiess, Andrej Nikolai ; Kellokumpu, Sakari ; Stanley, Pamela. / GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain. In: eLife. 2015 ; Vol. 4, No. September2015.
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