Functions of actin-interacting protein 1 (AIP1)/WD repeat protein 1 (WDR1) in actin filament dynamics and cytoskeletal regulation.

Actin-depolymerizing factor (ADF)/cofilin and actin-interacting protein 1 (AIP1), also known as WD-repeat protein 1 (WDR1), are conserved among eukaryotes and play critical roles in dynamic reorganization of the actin cytoskeleton. AIP1 preferentially promotes disassembly of ADF/cofilin-decorated actin filaments but exhibits minimal effects on bare actin filaments. Therefore, AIP1 has been often considered to be an ancillary co-factor of ADF/cofilin that merely boosts ADF/cofilin activity level. However, genetic and cell biological studies show that AIP1 deficiency often causes lethality or severe abnormalities in multiple tissues and organs including muscle, epithelia, and blood, suggesting that AIP1 is a major regulator of many biological processes that depend on actin dynamics. This review summarizes recent progress in studies on the biochemical mechanism of actin filament severing by AIP1 and in vivo functions of AIP1 in model organisms and human diseases.