title: Mouse profilin 2 regulates endocytosis and competes with SH3 ligand binding to dynamin 1.
abstract: Mammalian profilins are abundantly expressed actin monomer-binding proteins, highly conserved with respect to their affinities for G-actin, poly-L-proline, and phosphoinositides. Profilins associate with a large number of proline-rich proteins; the physiological significance and regulation of which is poorly understood. Here we show that profilin 2 associates with dynamin 1 via the C-terminal proline-rich domain of dynamin and thereby competes with the binding of SH3 ligands such as endophilin, amphiphysin, and Grb2, thus interfering with the assembly of the endocytic machinery. We also present a novel role for the brain-specific mouse profilin 2 as a regulator of membrane trafficking. Overexpression of profilin 2 inhibits endocytosis, whereas lack of profilin 2 in neurons results in an increase in endocytosis and membrane recycling. Phosphatidylinositol 4,5-bisphosphate releases profilin 2 from the profilin 2-dynamin 1 complex as well as from the profilin 2-actin complex, suggesting that profilin 2 is diverging the phosphoinositide signaling pathway to actin polymerization as well as endocytosis.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Campus Adriano Buzzati-Traverso, 00016 Monterotondo, Italy.
authors.forename: Ralph
authors.initials: R
authors.lastname: Gareus
authors.forename: Alessia
authors.initials: A
authors.lastname: Di Nardo
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rybin
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D034284:Dynamin I / Q000378:metabolism*; D004705:Endocytosis; D008024:Ligands; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D051304:Profilins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D000199:Actins; D008024:Ligands; D046912:Multiprotein Complexes; C495742:Pfn2 protein, mouse; D019269:Phosphatidylinositol 4,5-Diphosphate; D051304:Profilins; D034284:Dynamin I