The Glyco-enzyme adaptor GOLPH3 Links Intra-Golgi Transport Dynamics to Glycosylation Patterns and Cell Proliferation

Riccardo Rizzo , Domenico Russo , Kazuo Kurokawa , Pranoy Sahu , Bernadette Lombardi , Domenico Supino , Mikhail Zhukovsky , Anthony Vocat , Prathyush Pothukuchi , Vidya Kunnathully , Laura Capolupo , Gaëlle Boncompain (1, 2) , Carlo Vitagliano , Federica Zito Marino , Gabriella Aquino , Daniela Montariello , Petra Henklein , Luigi Mandrich , Gerardo Botti , Henrik Clausen , Ulla Mandel , Toshiyuki Yamaji , Kentaro Hanada , Alfredo Budillon , Franck Perez (1, 2) , Seetharaman Parashuraman , Yusuf Hannun , Akihiko Nakano , Daniela Corda , Giovanni D’angelo , Alberto Luini (3)

1 Institut Curie [Paris]
2 Biologie Cellulaire et Cancer
3 CNR - National Research Council of Italy | Consiglio Nazionale delle Ricerche

Glycans are ubiquitous sugar polymers with major biological functions that are assembled by glyco-enzymes onto cargo molecules during their transport through the Golgi complex. How the Golgi determines glycan assembly is poorly understood. By relying on the Golgi cisternal maturation model and using the glyco-enzyme adaptor and oncoprotein GOLPH3 as a molecular tool, we define the first example of how the Golgi controls glycosylation and associated cell functions. GOLPH3, acting as a component of the cisternal maturation mechanism, selectively binds and recycles a subset of glyco-enzymes of the glycosphingolipid synthetic pathway, hinders their escape to the lysosomes and hence increases their levels through a novel lysosomal degradation-regulated mechanism. This enhances the production of specific growth-inducing glycosphingolipids and reprograms the glycosphingolipid pathway to potentiate mitogenic signaling and cell proliferation. These findings unravel unforeseen organizing principles of Golgi-dependent glycosylation and delineate a paradigm for glycan assembly by the Golgi transport mechanisms. Moreover, they indicate a new role of cisternal maturation as a regulator of glycosylation, and outline a novel mechanism of action for GOLPH3-induced proliferation.

Domaines: Sciences du Vivant [q-bio]

Riccardo Rizzo, Domenico Russo, Kazuo Kurokawa, Pranoy Sahu, Bernadette Lombardi, et al.. The Glyco-enzyme adaptor GOLPH3 Links Intra-Golgi Transport Dynamics to Glycosylation Patterns and Cell Proliferation. 2020. ⟨hal-03007792⟩