Abstract 1203 Role of Phosphatidylserine in Mediating HSPA1A Membrane Localization during the Heat Shock Response

HSPA1A, a key molecular chaperone in cellular stress response and cancer cell survival, has established cytosolic functions but relocates to the plasma membrane (PM) in heat-shocked and cancer cells. This PM localization enhances immune modulation and cell survival, facilitated by HSPA1A's high affinity for phosphatidylserine (PS). While PS binding is linked to HSPA1A's membrane targeting, this interaction's specificity and mechanistic details remain incompletely understood. We hypothesized that PS functions as a primary driver of HSPA1A's PM translocation and that heat-induced PS elevation is critical in initiating this localization.