Comprehensive identification of plasma membrane repair proteins revealed spatiotemporal cellular responses to plasma membrane damage

Damage to the plasma membrane (PM) is common in all types of cells. PM repair processes, including exocytosis and endocytosis, are not mutually exclusive; rather, they collaborate to repair the wound. However, the temporal coordination between the repair processes remains poorly understood. Here, by comprehensively identifying PM repair proteins, we resolved the temporal PM repair processes at the damage site in Saccharomyces cerevisiae . Of the 80 repair proteins identified, 72 proteins were previously unreported repair protein candidates. We showed that polarity establishment, polarized exocytosis, and clathrin-mediated endocytosis (CME) occur in a specific temporal order at the damage site. Furthermore, we showed that polarized exocytosis and CME are coupled at the damage site, delivering PM repair proteins with transmembrane domains between the growing bud site and the damage site. This study provides insights into the temporal dynamics of coordinated cellular response to PM damage.