Ryan Vignogna
@rvig.bsky.social
Postdoc @fromme-lab.bsky.social | Heja BVB
We tested one of those candidates, DENND6A, and found that it indeed possesses strong GAP activity towards the Arf-like GTPase ARL8B:
January 6, 2026 at 3:38 PM
We tested one of those candidates, DENND6A, and found that it indeed possesses strong GAP activity towards the Arf-like GTPase ARL8B:
Based 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:
We predicted that other yeast (Anr2 + Afi1) and human (DENND11 + DENND6A/B) proteins are likely Arf-GAPs:
January 6, 2026 at 3:38 PM
Based 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:
We predicted that other yeast (Anr2 + Afi1) and human (DENND11 + DENND6A/B) proteins are likely Arf-GAPs:
Avl9 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:
Mutation of the predicted catalytic arginine in human AVL9 abolishes its ability to promote cell migration, linking its enzymatic activity to cancer physiology:
January 6, 2026 at 3:38 PM
Avl9 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:
Mutation of the predicted catalytic arginine in human AVL9 abolishes its ability to promote cell migration, linking its enzymatic activity to cancer physiology:
Additional 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:
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:
January 6, 2026 at 3:38 PM
Additional 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:
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:
Biochemical assays confirmed this prediction.
Avl9 exhibits robust GAP activity toward Arf-family GTPases, with highest activity toward Arf1:
Avl9 exhibits robust GAP activity toward Arf-family GTPases, with highest activity toward Arf1:
January 6, 2026 at 3:38 PM
Biochemical assays confirmed this prediction.
Avl9 exhibits robust GAP activity toward Arf-family GTPases, with highest activity toward Arf1:
Avl9 exhibits robust GAP activity toward Arf-family GTPases, with highest activity toward Arf1:
Using 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:
January 6, 2026 at 3:38 PM
Using 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: