Enteropathogenic E. coli relies on collaboration between the formin mDia1 and the Arp2/3 complex for actin pedestal biogenesis and maintenance
Fig 9
Model for mDia1 functions in EPEC pedestals.
(A) We propose that mDia1 activity at the base of the pedestal assembles linear actin filaments, which can be used as mother filaments by the Arp2/3 complex to generate a densely branched network towards the pedestal tip. In the absence of mDia1, pedestals are less numerous and weaker due to fewer seed filaments and lower levels of Tir phosphorylation. In the absence of the Arp2/3 complex, any actin that is nucleated by mDia1 (as weak puncta or actin baskets) is unable to be reorganized and focused into a pedestal. See Discussion for details. (B) A previously established signaling pathway for pedestal formation (black solid arrows) is driven by Tir clustering, tyrosine phosphorylation by Src and Abl family kinases, recruitment of Nck1/2 and N-WASP, and activation of the Arp2/3 complex to polymerize branched actin networks. Our current results expand on this model to include (1) mDia1-associated actin assembly (blue solid arrow) possibly providing seed filaments for the Arp2/3 complex (blue dashed arrow), and (2) mDia1-mediated enhancement of Src activation in pedestals (blue solid arrow) to promote and sustain Tir phosphorylation. It is unclear if mDia1 is recruited by SFKs, pY474, or the Arp2/3 complex, or if Arp2/3-based actin networks that disassemble at the base of the pedestal are recycled by mDia1 (gray dashed arrows). See Discussion for details.