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bioRxiv · 10.1101/2020.05.05.078097

PARP12-catalyzed mono-ADP-ribosylation of Golgin-97 controls the transport of E-cadherin

Grimaldi, G.·Schembri, L.·Lo Monte, M.·Spano, D.·Di Martino, R.·Beccari, A. R.·Valente, C.·Corda, D.
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Abstract

ADP-ribosylation is a post-translational modification involved in physiological and pathological events catalyzed by Poly-ADP-Ribosyl-Polymerase (PARP) enzymes. Substrates of this reaction have been identified by mass-spectrometry, but the definition of PARPs-regulated cellular functions remains scarce. Here, we have analyzed the control of intracellular membrane traffic by the mono-ADP-ribosyl-transferase PARP12, motivated by its localization at the trans-Golgi network. By using bioinformatics, mutagenesis and cell biology approaches we identified Golgin-97, a protein regulating exocytosis, as a PARP12-specific substrate. Mono-ADP-ribosylation of Golgin-97 residues E558-E559-E565 is required for supporting traffic from the trans-Golgi network to the plasma membrane. This step is halted when PARP12 is deleted or when the Golgin-97 ADP-ribosylation-defective mutant is expressed. Under these conditions E-cadherin, whose transport is controlled by Golgin-97, does not reach the plasma membrane but accumulates in a trans-Golgi proximal compartment. Thus, we demonstrate that the ADP-ribosylation of Golgin-97 is required for E-cadherin exocytosis and thus this event may regulate the sorting of exocytic carriers as well as epithelial-to-mesenchymal transition.

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Grimaldi, G., Schembri, L., Lo Monte, M., Spano, D., Di Martino, R., Beccari, A. R., Valente, C., Corda, D.. 2020-05-05. PARP12-catalyzed mono-ADP-ribosylation of Golgin-97 controls the transport of E-cadherin. https://doi.org/10.1101/2020.05.05.078097

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