Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis.
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.
Department of Microbiology and Molecular Genetics, University of California, Irvine, United States.
Haik
H
Mkhikian
Department of Microbiology and Molecular Genetics, University of California, Irvine, United States.
Christie-Lynn
CL
Mortales
Department of Neurology and Institute for Immunology, University of California, Irvine, United States.
Raymond W
RW
Zhou
Department of Microbiology and Molecular Genetics, University of California, Irvine, United States.
Khachik
K
Khachikyan
Department of Life Sciences, Imperial College London, London, United Kingdom.
Gang
G
Wu
Department of Life Sciences, Imperial College London, London, United Kingdom.
Stuart M
SM
Haslam
Department of Microbiology and Molecular Genetics, University of California, Irvine, United States.
Patil
P
Kavarian
Department of Life Sciences, Imperial College London, London, United Kingdom.
Anne
A
Dell
Department of Microbiology and Molecular Genetics, University of California, Irvine, United States.|Department of Neurology and Institute for Immunology, University of California, Irvine, United States.
Michael
0000-0001-8547-5774
M
Demetriou
D000818:Animals; D002478:Cells, Cultured; D037161:Galectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006706:Homeostasis; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000378:metabolism*
D037161:Galectins; D006023:Glycoproteins; D011134:Polysaccharides
Golgi; N-glycosylation; T cell; biochemistry; bioequivalence; cell biology; galectin; human; mouse; self-correction