Ryan Vignogna @rvig.bsky.social · 09/09/2026Also please enjoy my family and friends’ responses to this paper 010
Reposted by Ryan VignognaWeill Institute for Cell & Molecular Biology @weillinstitute.bsky.social · 09/09/2026@weillinstitute.bsky.social adventures with AI from @fromme-lab.bsky.social! @rvig.bsky.social and colleagues used AI to uncover a previously unknown class of cellular “off switches” that regulate protein trafficking, revealing new insights into pathways linked to cancer cell movement and disease.news.cornell.eduAI reveals new class of cellular ‘off switch’ linked to cancer pathways | Cornell ChronicleCornell researchers have used artificial intelligence to uncover a previously unknown way cells control how proteins move inside them, a process essential for growth, communication and movement, and o... 021
Ryan Vignogna @rvig.bsky.social · 09/09/2026🎉 Our DENN GAP paper is now out in JCB! Some exciting new results were added since the preprint, including the discovery that yeast and human AVL9 differ in substrate specificity. rupress.org/jcb/article/...rupress.orgAvl9 defines a family of DENN domain GTPase-activating proteinsUsing computational protein–protein interaction screens, Vignogna and Fromme identify Avl9 as a GTPase-activating protein for Arf-family GTPases. They demo 184
Ryan Vignogna @rvig.bsky.social · 26/08/2026weird...shows up if you search for the DOI, but it still leads to a dead page 100
Ryan Vignogna @rvig.bsky.social · 06/01/2026I owe a very special thanks to Shiying Huang and all members of the Baskin Lab (@jeremybaskin.bsky.social) for helping this yeasty boy learn the ins and outs of cell culture. (end) 020
Ryan Vignogna @rvig.bsky.social · 06/01/2026More broadly, I think this work is a nice example of the power of AlphaFold in identifying both previously-unknown protein-protein interactions and protein functions. 110
Ryan Vignogna @rvig.bsky.social · 06/01/2026Overall, this work identifies a new class of monomeric “DENN GAP” proteins, with Avl9 and DENND6A as its founding members. Future work is aimed at determining the substrates and biological roles of the remaining DENN GAPs. 120
Ryan Vignogna @rvig.bsky.social · 06/01/2026We tested one of those candidates, DENND6A, and found that it indeed possesses strong GAP activity towards the Arf-like GTPase ARL8B: 100
Ryan Vignogna @rvig.bsky.social · 06/01/2026Based on these findings, we predicted that other monomeric DENN domain proteins may be Arf-GAPs. We predicted that other yeast (Anr2 + Afi1) and human (DENND11 + DENND6A/B) proteins are likely Arf-GAPs: 100
Ryan Vignogna @rvig.bsky.social · 06/01/2026Avl9 GAP function is (likely) conserved in humans. Mutation of the predicted catalytic arginine in human AVL9 abolishes its ability to promote cell migration, linking its enzymatic activity to cancer physiology: 110
Ryan Vignogna @rvig.bsky.social · 06/01/2026Additional structural predictions hinted that Avl9 also interacts with a Rab. We found that Avl9 localization is mediated by Rab8, which binds a distinct, non-catalytic surface of Avl9. Rab8 recruitment strongly enhances Avl9’s Arf1-GAP activity on membranes: 100
Ryan Vignogna @rvig.bsky.social · 06/01/2026Biochemical assays confirmed this prediction. Avl9 exhibits robust GAP activity toward Arf-family GTPases, with highest activity toward Arf1: 100
Ryan Vignogna @rvig.bsky.social · 06/01/2026Using large-scale AlphaFold-multimer–based interaction screens, we identified a high-confidence interaction between Arf1 and Avl9. The predicted interaction resembles that of a GTPase–GAP interaction, with a conserved arginine finger of Avl9 pointed at Arf-bound GTP: 100
Ryan Vignogna @rvig.bsky.social · 06/01/2026Monomeric DENN domain proteins are widely thought to function solely as Rab-GEFs, yet the molecular function of Avl9 has remained unclear despite its role in secretion and cell migration. 110
Ryan Vignogna @rvig.bsky.social · 06/01/2026Mind the GAP 🚧🕳️🚧 Excited to share the latest preprint from the Fromme Lab (@fromme-lab.bsky.social), showing that the DENN domain protein Avl9 functions as an Arf-GAP, revising long-standing assumptions about DENN protein function, 🧵: www.biorxiv.org/content/10.6...biorxiv.orgAvl9 defines a family of GTPase-activating proteins that regulate diverse cell biological functionsRas-related GTPases are molecular switches regulating hundreds of signaling and trafficking pathways in cells. Many GTPase regulators remain to be identified despite extensive genetic and biochemical ... 1175
Reposted by Ryan VignognaFromme Lab @fromme-lab.bsky.social · 04/12/2024Excited to share the published version of our work by @ryanfeathers.bsky.social and @rvig.bsky.social on the structural basis for activation of Rab6 by the Ric1-Rgp1 complex! rdcu.be/d2mu3 Here is an updated thread about the paper we first shared on that older platform when we posted the preprint 1398
