Disease relevance of Actr2

• RNA interference silencing of up to 90% of Arp3 protein expression, a major subunit of the Arp2/3 complex, proportionately decreases the intracellular motility of Listeria monocytogenes and actin nucleation activity ascribable to the Arp2/3 complex in mouse embryonic fibroblasts [1].
• Cellular proteins essential for actin polymerization downstream of Rho family GTPases include the Arp2/3 complex as an actin nucleator and members of the Wiskott-Aldrich Syndrome protein (WASP) family as activators of the Arp2/3 complex [2].

High impact information on Actr2

• Significantly, alpha-catenin directly regulates actin-filament organization by suppressing Arp2/3-mediated actin polymerization, likely by competing with the Arp2/3 complex for binding to actin filaments [3].
• In addition, a Rac1/2 or Vav1/3 deficiency blocks Arp2/3 recruitment and actin polymerization at the complement-induced phagosome, indicating that these proteins regulate early steps in phagocytosis [4].
• We propose that constitutive VCA domain phosphorylation is required for optimal stimulation of the Arp2/3 complex by WASP [5].
• Arp2/3 inhibition in fibroblasts severely disrupts actin organization and membrane protrusion [6].
• In contrast, Arp2/3 inhibition in growth cones minimally affects actin organization and does not inhibit lamellipodia protrusion or de novo filopodia formation [6].

Associations of Actr2 with chemical compounds

• This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery [7].

Biological context of Actr2

• We suggest that N-WASP and the Arp2/3 complex trigger actin polymerization during a late step in clathrin-mediated endocytosis, and propel clathrin-coated pits or vesicles from the plasma membrane into the cytoplasm [8].
• In NIH 3T3 cells, we found that actin and Arp2/3 complex contributed to cell polarity establishment [2].
• We therefore analyzed the involvement of the Arp2/3 complex and WASP-family proteins in in vitro wound healing assays using NIH 3T3 fibroblasts and astrocytes [2].
• Src family kinases activate N-WASP through tyrosine phosphorylation, which induces Arp2/3 complex-mediated actin polymerization [9].
• Cell migration is driven by actin polymerization at the leading edge of lamellipodia, where WASP family verprolin-homologous proteins (WAVEs) activate Arp2/3 complex [10].

Anatomical context of Actr2

• Neural Wiskott Aldrich Syndrome Protein (N-WASP) and the Arp2/3 complex are recruited to sites of clathrin-mediated endocytosis in cultured fibroblasts [8].
• Surprisingly, Arp2/3 inhibition significantly enhances axon elongation and causes defects in growth cone guidance [6].
• Arp2/3 is an actin binding complex that is enriched in the peripheral lamellipodia of fibroblasts, where it forms a network of short, branched actin filaments, generating the protrusive force that extends lamellipodia and drives fibroblast motility [6].
• Although it has been assumed that Arp2/3 would play a similar role in growth cones, our studies indicate that Arp2/3 is enriched in the central, not the peripheral, region of growth cones and that the growth cone periphery contains few branched actin filaments [6].
• Furthermore, in NIH 3T3 cells, Scar2 and the Arp2/3 complex appear to be involved in the establishment and maintenance of Golgi polarity during directed migration [2].

Regulatory relationships of Actr2

• N-WASP activates Arp2/3 complex-dependent actin polymerization through the VCA region, leading to filopodium formation [11].

Other interactions of Actr2

• We find that Arp3, a component of the Arp2/3 complex, appears transiently while single clathrin-coated pits internalize [8].
• WAVE1 has been reported to associate and activate Arp2/3 complex at its C-terminal region that is rich in acidic residues [12].
• This protein has a VCA region (verplorin-like, cofilin-like, acidic region) at the C-terminus, which binds to G-actin and Arp2/3 complex, and several functional domains at the N-terminus, such as WHD (WASP homology domain) and GBD/CRIB domain [11].

References