HIV Assembly and Budding: Ca²⁺ Signaling and Non-ESCRT Proteins Set the Stage

Figure 3

Ca²⁺ facilitates Gag-PI(4,5)P₂ interaction and stabilization on the plasma membrane. Top, the squares highlight the top-down view of the plasma membrane shown below. Bottom, (1) most of the PI(4,5)P₂ on the plasma-membrane is sequestered with plasma membrane-resident proteins that are highly basic and therefore unavailable to Gag. (2) A local rise in Ca²⁺ permits the cation to replace the resident proteins, freeing the PI(4,5)P₂ from these proteins. (3) PI(4,5)P₂, made available by Ca²⁺, recruits Gag to the plasma membrane. (4) Gag multimerization forms local PIP2 clusters that stabilize Gag association with the membrane, preventing loss of Gag from the narrowing bud neck in preparation for ESCRT recruitment.