Early and nonredundant functions of dynamin isoforms in clathrin-mediated endocytosis.

摘要: Dynamin GTPases (Dyn1 and Dyn2) are indispensable proteins of the core clathrin-mediated endocytosis (CME) machinery. Best known for their role in fission at late stages CME, many studies have suggested that dynamin also plays a regulatory during early CME; however, detailed regarding isoform-specific functions dynamins lacking. With recent understanding regulation Dyn1 nonneuronal cells improved algorithms highly sensitive quantitative analysis clathrin-coated pit (CCP) dynamics, we evaluated differential isoforms CME using domain swap chimeras. We report Dyn2 play nonredundant, roles cells. The proline/arginine-rich is important its targeting to nascent growing CCPs, whereas membrane-binding curvature-generating pleckstrin homology an stabilizing CCPs. confirm enhanced ability dephosphorylated support even substoichiometric levels compared with Dyn2. Domain chimeras revealed previously unknown functional differences GTPase stalk domains. Our study significantly extends current played by CME.