Gelsolin: Calcium‐ and polyphosphoinositide‐regulated actin‐ modulating protein

Abstract

Receptor‐mediated stimulation induces massive actin polymerization and cyto‐skeletal reorganization. The activity of a potent actin‐modulating protein, gelsolin, is regulated both by Ca²⁺ and polyphos‐phoinositides, and it may have a pivotal role in restructuring the actin cytoskeleton in response to agonist stimulation. Structure‐function analysis of gelsolin has (1) indicated that its NH₂‐terminal half is primarily responsible for modulating actin filament length and polymerization; and (2) elucidated mechanisms by which Ca²⁺ and phospholipids may regulate such functions. Gelsolin is functionally and structurally similar to villin, another Ca²⁺‐activated actin‐severing protein found in microvilli, suggesting that gelsolin may be a prototype of this family of actin‐modulating proteins. A molecular variant of gelsolin is secreted and may be involved in the clearance of actin filaments released during tissue damage. The two forms of gelsolin are encoded by a single gene, and distinct messages are derived by alternative message splicing.