A Novel Ca 2 1 - binding Protein , p 22 , Is Required for Constitutive Membrane

We have identified a novel protein, p22, required for “constitutive” exocytic membrane traffic. p22 belongs to the EF-hand superfamily of Ca-binding proteins and shows extensive similarity to the regulatory subunit of protein phosphatase 2B, calcineurin B. p22 is a cytosolic N-myristoylated protein that undergoes conformational changes upon binding of Ca. Antibodies against a p22 peptide block the targeting/fusion of transcytotic vesicles with the apical plasma membrane, but recombinant wild-type p22 overcomes that inhibition. Nonmyristoylated p22, or p22 incapable of undergoing Ca-induced conformational changes, cannot reverse the antibodymediated inhibition. The data suggest that p22 may act by transducing cellular Ca signals to downstream effectors. p22 is ubiquitously expressed, and we propose that its function is required for membrane trafficking events common to many cells.