EPFL BioE Talks SERIES "GOLPH3 Coordinates Glycosphingolipid Metabolism at the Golgi Complex"

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Date and time 05.10.2020 16:3017:00  
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Speaker Prof. Giovanni D'Angelo, Institute of Bioengineering, EPFL, Lausanne (CH)
Category Conferences - Seminars
WEEKLY EPFL BIOE TALKS SERIES

(note that this talk is number two of a double-feature seminar - see details of the first talk here)

Abstract:
The Golgi apparatus is a hub for several metabolic pathways including those involving glycan and lipid syntheses. These metabolisms rely on competing reactions catalysed by Golgi-resident enzymes during the passage of substrates through the Golgi cisternae. While the relative position of the enzymes within the Golgi stack determines the reaction sequence and the metabolic output, the mechanisms that coordinate the intra-Golgi localization of the enzymes are poorly understood. Here, we studied GOLPH3, an oncoprotein with a reported role in Golgi enzymes localization. We found that GOLPH3 binds to and regulates multiple sequentially-acting enzymes of the glycosphingolipid synthesis. GOLPH3 drives their dynamic localisation at the trans Golgi, counteracts their transport to lysosomes and consequent degradation. Through these effects, increased GOLPH3 levels, as those observed in solid tumours, foster glycosphingolipid production and exposure at the external leaflet of the plasma membrane. Here, glycosphingolipids promote mitogenic signalling and cell proliferation. Our findings unravel the mechanisms by which Golgi recycling drives the localization of specific enzymes in the appropriate cisternae, their degradation rate, and their organization into functional modules that impact distinctive metabolic pathways. Moreover, our data have medical implications as they outline a novel oncogenic mechanism of action for GOLPH3 based on glycosphingolipid metabolism.


Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks


IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 situation, this seminar can be followed via Zoom web-streaming only, following prior one-time registration through the link above.

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