Enlightening endocytic membrane dynamics
1 Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Roessle-Straße 10, 13125 Berlin, Germany;
2 Freie Universität Berlin, Department of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany,
3 NeuroCure Cluster of Excellence
Biological membranes undergo constant remodeling by membrane fission and fusion to change their shape, to exchange material between subcellular compartments, or to spatiotemporally control cell signaling including neurotransmission at neuronal synapses. A prime example is the formation of endocytic vesicles by clathrin-mediated endocytosis CME) at the plasma membrane. CME, an essential process for plasma membrane homeostasis and cell signaling, is characterized by a stunning heterogeneity in the size and lifetime of clathrin-coated endocytic pits (CCPs). If and how CCP growth and lifetime are coupled and how this relates to their physiological function is unknown. In my talk I will report on our most recent studies that combine automated tracking of CCP dynamics, electron microscopy, and functional rescue experiments to demonstrate that CCP growth and lifetime are closely correlated and mechanistically linked by the early-acting endocytic F-BAR protein FCHo2. FCHo2 assembles at the rim of CCPs to control CCP growth and lifetime by coupling the invagination of early endocytic intermediates to clathrin lattice assembly. Our data suggest a mechanism for the nanoscale control of CCP growth and stability that may similarly apply to other metastable structures in cells.