
@article {99331,
	title = {GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis},
	journal = {EMBO JOURNAL},
	year = {2021},
	month = {09/2021},
	pages = {e107766},
	abstract = {<p>The Golgi apparatus, the main glycosylation station of the cell, consists of a stack of discontinuous cisternae. Glycosylation enzymes are usually concentrated in one or two specific cisternae along the cis-trans axis of the organelle. How such compartmentalized localization of enzymes is achieved and how it contributes to glycosylation are not clear. Here, we show that the Golgi matrix protein GRASP55 directs the compartmentalized localization of key enzymes involved in glycosphingolipid (GSL) biosynthesis. GRASP55 binds to these enzymes and prevents their entry into COPI-based retrograde transport vesicles, thus concentrating them in the trans-Golgi. In genome-edited cells lacking GRASP55, or in cells expressing mutant enzymes without GRASP55 binding sites, these enzymes relocate to the cis-Golgi, which affects glycosphingolipid biosynthesis by changing flux across metabolic branch points. These findings reveal a mechanism by which a matrix protein regulates polarized localization of glycosylation enzymes in the Golgi and controls competition in glycan biosynthesis.</p>
},
	doi = {10.15252/embj.2021107766},
	author = {Pothukuchi, Prathyush and Agliarulo, Ilenia and Pirozzi, Marinella and Rizzo, Riccardo and Russo, Domenico and Turacchio, Gabriele and Nuechel, Julian and Yang, Jia-Shu and Gehin, Charlotte and Capolupo, Laura and Hernandez-Corbacho, Maria Jose and Biswas, Ansuman and Vanacore, Giovanna and Dathan, Nina and Nitta, Takahiro and Henklein, Petra and Thattai, Mukund and Inokuchi, Jin-Ichi and Hsu, Victor W. and Plomann, Markus and Obeid, Lina M and Hannun, Yusuf A. and Luini, Alberto and D{\textquoteright}Angelo, Giovanni and Parashuraman, Seetharaman}
}
@article {78112,
	title = {Promiscuity and specificity of eukaryotic glycosyltransferases.},
	journal = {Biochem Soc Trans},
	year = {2020},
	month = {2020 Jun 15},
	abstract = {<p>Glycosyltransferases are a large family of enzymes responsible for covalently linking sugar monosaccharides to a variety of organic substrates. These enzymes drive the synthesis of complex oligosaccharides known as glycans, which play key roles in inter-cellular interactions across all the kingdoms of life; they also catalyze sugar attachment during the synthesis of small-molecule metabolites such as plant flavonoids. A given glycosyltransferase enzyme is typically responsible for attaching a specific donor monosaccharide, via a specific glycosidic linkage, to a specific moiety on the acceptor substrate. However these enzymes are often promiscuous, able catalyze linkages between a variety of donors and acceptors. In this review we discuss distinct classes of glycosyltransferase promiscuity, each illustrated by enzymatic examples from small-molecule or glycan synthesis. We highlight the physical causes of promiscuity, and its biochemical consequences. Structural studies of glycosyltransferases involved in glycan synthesis show that they make specific contacts with {\textquoteright}recognition motifs{\textquoteright} that are much smaller than the full oligosaccharide substrate. There is a wide range in the sizes of glycosyltransferase recognition motifs: highly promiscuous enzymes recognize monosaccharide or disaccharide motifs across multiple oligosaccharides, while highly specific enzymes recognize large, complex motifs found on few oligosaccharides. In eukaryotes, the localization of glycosyltransferases within compartments of the Golgi apparatus may play a role in mitigating the glycan variability caused by enzyme promiscuity.</p>
},
	issn = {1470-8752},
	doi = {10.1042/BST20190651},
	author = {Biswas, Ansuman and Thattai, Mukund}
}
