Poster Presentation 11th International Symposium on Autophagy 2025

WBP2 connects Vesicle-Coat Proteins and Autophagosome Maturation (#236)

Stephanie Kaeser-Pebernard 1 , Jianwen Zhou 2 , Christine Vionnet 1 , Muriel Mari 3 , Roger Schneiter 1 , Stefano Vanni 1 , Fulvio Reggiori 3 , Jörn Dengjel 1
  1. University of Fribourg, FRIBOURG, Switzerland
  2. ETHZ, Zurich, Switzerland
  3. Department of biomedicine, Aarhus University, Aarhus, Denmark

Macroautophagy is a catabolic process in which double-membrane vesicles, autophagosomes, are newly formed to engulf intracellular substrates or pathogens and deliver them to lysosomes for subsequent degradation. Whereas key molecular players and mechanisms involved in autophagosome formation have been discovered, mechanisms of membrane recruitment for the formation of nascent autophagosomes are still not fully understood. Here, we performed unbiased mass spectrometry-based organellar proteomics and identified the oncogene WBP2 as a positive regulator of autophagosome formation. In contrast to its nuclear function as transcriptional coactivator, cytoplasmic WBP2 binds to phosphatidylinositiol phosphate-containing lipids via its GRAM domain and orchestrates vesicle recruitment to growing autophagosomes via its C-terminal KKXX motif. WBP2 negative cells exhibit high levels of basal autophagosome initiation events, and abnormal elongated phagophore structures which are still connected to the ER. We propose that WBP2 is a new lipid-binding protein which plays a crucial role in maturation of nascent autophagosomes.