PKD-dependent PARP12-catalyzed mono-ADP-ribosylation of Golgin-97 is required for E-cadherin transport from Golgi to plasma membrane

Proc Natl Acad Sci U S A. 2022 Jan 4;119(1):e2026494119. doi: 10.1073/pnas.2026494119.


Adenosine diphosphate (ADP)-ribosylation is a posttranslational modification involved in key regulatory events catalyzed by ADP-ribosyltransferases (ARTs). Substrate identification and localization of the mono-ADP-ribosyltransferase PARP12 at the trans-Golgi network (TGN) hinted at the involvement of ARTs in intracellular traffic. We find that Golgin-97, a TGN protein required for the formation and transport of a specific class of basolateral cargoes (e.g., E-cadherin and vesicular stomatitis virus G protein [VSVG]), is a PARP12 substrate. PARP12 targets an acidic cluster in the Golgin-97 coiled-coil domain essential for function. Its mutation or PARP12 depletion, delays E-cadherin and VSVG export and leads to a defect in carrier fission, hence in transport, with consequent accumulation of cargoes in a trans-Golgi/Rab11-positive intermediate compartment. In contrast, PARP12 does not control the Golgin-245-dependent traffic of cargoes such as tumor necrosis factor alpha (TNFα). Thus, the transport of different basolateral proteins to the plasma membrane is differentially regulated by Golgin-97 mono-ADP-ribosylation by PARP12. This identifies a selective regulatory mechanism acting on the transport of Golgin-97- vs. Golgin-245-dependent cargoes. Of note, PARP12 enzymatic activity, and consequently Golgin-97 mono-ADP-ribosylation, depends on the activation of protein kinase D (PKD) at the TGN during traffic. PARP12 is directly phosphorylated by PKD, and this is essential to stimulate PARP12 catalytic activity. PARP12 is therefore a component of the PKD-driven regulatory cascade that selectively controls a major branch of the basolateral transport pathway. We propose that through this mechanism, PARP12 contributes to the maintenance of E-cadherin-mediated cell polarity and cell-cell junctions.

Keywords: E-cadherin; Golgin-97 ADP-ribosylation; PARP12; PKD; intracellular membrane transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation / physiology*
  • Antigens, CD
  • Autoantigens / metabolism*
  • Cadherins / metabolism*
  • Catalysis
  • Cell Membrane / metabolism*
  • Golgi Apparatus / metabolism*
  • Golgi Matrix Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Tumor Necrosis Factor-alpha
  • trans-Golgi Network / metabolism


  • Antigens, CD
  • Autoantigens
  • CDH1 protein, human
  • Cadherins
  • Golgi Matrix Proteins
  • Golgi complex autoantigen, 97-kDa
  • Tumor Necrosis Factor-alpha
  • Poly(ADP-ribose) Polymerases
  • protein kinase D
  • Protein Kinase C