actinnucleating

Actin nucleation, sometimes referred to as actin nucleating, is the initial step in the assembly of actin filaments in cells, where actin monomers (G-actin) form a stable nucleus that can rapidly elongate into filamentous actin (F-actin). Spontaneous nucleation of actin is energetically unfavorable in vivo, so cells employ dedicated nucleators to accelerate nucleus formation and regulate filament formation.

The principal actin nucleators fall into two broad categories. Arp2/3 complex–dependent nucleation uses nucleation-promoting factors (NPFs) such as WASP/WAVE proteins to activate the Arp2/3 complex, which creates a new branch from an existing filament, producing a branched, dendritic network. Formins promote linear actin filaments by nucleating and then processively associating with the growing barbed end, enabling rapid elongation. Other factors such as Spire, Leiomodin, and Cobl contribute to nucleation and filament assembly in specific cellular contexts and can cooperate with formins or Arp2/3 to shape different actin architectures.

Regulation of actin nucleation involves signaling pathways (for example, Rho family GTPases and phosphoinositides) that control nucleator activity, as well as actin-binding proteins that influence monomer availability (profilin) or nucleation efficiency (capping proteins, thymosin β4). The balance between nucleation, elongation, and disassembly determines the organization of the actin cytoskeleton, underpinning processes such as cell migration, endocytosis, vesicle trafficking, and cytokinesis.

In summary, actin nucleation is a controlled, rate-limiting step in cytoskeletal assembly, orchestrated by specialized nucleators and regulatory mechanisms to generate diverse actin structures.