A nucleator arms race: cellular control of actin assembly

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Abstract
The actin cytoskeleton has key roles in many dynamic cellular processes, such as cell shape changes, cell movement, cell division and membrane dynamics. Mammalian cells express numerous factors that nucleate actin filaments de novo, including the actin-related protein 2/3 (ARP2/3) complex and multiple nucleation-promoting factors (NPFs), ∼ 15 formins and several members of the Spire, Cordon-bleu and leiomodin families. Actin nucleators are regulated by distinct autoinhibitory and trans-inhibitory mechanisms and are directed to reorganize the cytoskeleton by their numerous protein and phospholipid binding partners. ARP2/3 generates branched filament networks at plasma membrane invaginations or protrusions in concert with NPFs from the Wiskott–Aldrich syndrome protein (WASP) and WASP-family verprolin homologue (WAVE; also known as SCAR) families, but also assembles actin at endosomes, along the endoplasmic reticulum–Golgi secretory pathway, and perhaps in the nucleus by cooperating with the recently identified NPFs: WASP and SCAR homologue (WASH), WASP homologue associated with actin, membranes and microtubules (WHAMM) and junction-mediating regulatory protein (JMY), respectively. Formins nucleate unbranched actin structures, facilitate filament elongation and sometimes bundle actin during plasma membrane protrusion, stress fibre formation and cell division. Nucleators from the Spire, Cordon-bleu and leiomodin families use multiple actin monomer-binding sequences to nucleate actin, and influence membrane transport, neuronal morphology and muscle cell organization, respectively.