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

EP2 Receptor Antagonist PF-04418948 Blocks Prostaglandin E2-Induction of Cyclooxygenase-2 and Decreases the Incidence of Experimental Necrotizing Enterocolitis

Surgical site occurrence (SSO) MRSA (+), n (%) (n1⁄436) M RSA (-), n (%) (n1⁄4585) p Value Seroma 7 (19.4) 84 (14.4) 0.402 Cellulitis 11 (30.6) 80 (13.7) 0.005 Serous drainage 8 (22.2) 50 (8.6) 0.006 Purulent drainage 5 (13.9) 25 (4.3) 0.009 Soft tissue necrosis 5 (13.9) 17 (2.9) 0.001 Unspecified SSO 2 (5.6) 18 (3.1) 0.414 Dehiscence 1 (2.8) 18 (3.1) 0.919 Hematoma 2 (5.6) 17 (2.9) 0.370 Enterocutaneous fistula 1 (2.8) 1 (0.2) 0.007 Vol. 221, No. 4S1, October 2015 Scientific Forum Abstracts S6