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Homeostatic control of cell growth and differentiation by Golgi proofreading
Author(s) -
Demetriou Michael,
Mkhikian Haik
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.211.3
Subject(s) - golgi apparatus , microbiology and biotechnology , chemistry , glycan , homeostasis , cell , glycoprotein , biology , biochemistry
Homeostatic proofreading is an essential feature of critical biological systems. Here we describe a homeostatic mechanism within the Golgi that controls cell growth and differentiation. Galectins bind N‐acetyllactosamine (LacNAc: Galâ1,4GlcNAc) in branched N‐glycans attached to surface glycoproteins, forming a molecular lattice that controls cell growth and differentiation by regulating receptor clustering/surface‐retention/signaling. LacNAc density and galectin avidity for N‐glycans increase proportional to the number of branches produced by the Golgi branching enzymes Mgat1, 2, 4, and 5. Mgat5 deficiency marginally reduces LacNAc content by limiting N‐glycans to three branches, yet results in Tcell hyperactivity and autoimmunity. Restricting N‐glycans to a single branch via Mgat2 deficiency or mannosidase II inhibition does not produce a more hyperactive state. Rather, a marked increase in poly‐LacNAc extension maintains galectin binding to N‐glycans, thereby preventing further enhancement of T cell activity; phenotypes reversed by deficiency of the poly‐LacNAc extension enzyme B3GnT2 or complete blockade of branching. Homeostatic maintenance of LacNAc levels is also present in epithelial and stem cells. These data define Golgi proofreading and LacNAc content, rather than unique N‐glycan structures, as critical regulators of the galectin lattice and cell homeostasis.