Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis
eLife, ISSN: 2050-084X, Vol: 5, Issue: JUNE2016, Page: e14814
2016
- 62Citations
- 70Captures
- 1Mentions
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Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis
Research Article ACCEPTED MANUSCRIPT Haik Mkhikian Christie-Lynn Mortales Raymond Zhou Khachik Khachikyan Gang Wu Stuart M Haslam Patil Kavarian Anne Dell Michael Demetriou University of
Article Description
Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N-glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme β1,3-N-acetylglucosaminyltransferase (B3GNT). Marginally reducing LacNAc content by limiting N-glycans to three branches results in T-cell hyperactivity and autoimmunity; yet further restricting branching does not produce a more hyperactive state. Rather, new poly-LacNAc extension by B3GNT maintains galectin binding and immune homeostasis. Poly-LacNAc extension is triggered by redistribution of unused UDP-GlcNAc from the medial to trans-Golgi via inter-cisternal tubules. These data demonstrate the functional equivalency of structurally dissimilar N-glycans and suggest a self-correcting feature of the Golgi that sustains cellular homeostasis.
Bibliographic Details
10.7554/elife.14814; 10.7554/elife.14814.017; 10.7554/elife.14814.005; 10.7554/elife.14814.001; 10.7554/elife.14814.011; 10.7554/elife.14814.002; 10.7554/elife.14814.013; 10.7554/elife.14814.019; 10.7554/elife.14814.021; 10.7554/elife.14814.020; 10.7554/elife.14814.015; 10.7554/elife.14814.014; 10.7554/elife.14814.009; 10.7554/elife.14814.003
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