The Glyco-enzyme adaptor GOLPH3 Links Intra-Golgi Transport Dynamics to Glycosylation Patterns and Cell Proliferation - Archive ouverte HAL Access content directly
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The Glyco-enzyme adaptor GOLPH3 Links Intra-Golgi Transport Dynamics to Glycosylation Patterns and Cell Proliferation

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

Abstract

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.
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hal-03007792 , version 1 (16-11-2020)

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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⟩
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