Functional implications of Pacsin2 localization in mast cells

Abstract

Mast cell activation and degranulation involves rapid and dramatic reorganization of plasma membrane and cytoskeleton. We discovered that the protein Pacsin2 (syndapin II) localizes in distinct ring-like structures on resting mast cell plasma membranes. These rings surround areas of high F-actin and plasma membrane signals, resembling reservoirs. Activation through FCER1 or thapsigargin rapidly disassemble Pacsin2 rings and reservoirs, which reform when activation ceases. Localization of Pacsin2 to rings is dependent on the F-BAR domain region of the protein, which is responsible for plasma membrane bending and curvature sensing. Pacsin2 ring formation is anti-correlated with the activity of N-WASP, an Arp2/3-activating protein that promotes F-actin assembly and degranulation downstream of FCER1. Notably, N-WASP inhibition increases Pacsin2 localization at the plasma membrane. Due to its dynamic ring-like organization at membrane reservoirs and opposing relationship to N-WASP during cell activation, Pacsin2 may serve as a conduit between structural organization of the plasma membrane and downstream signaling to impact mast cell functions such as degranulation.