| First Author | Lian G | Year | 2016 |
| Journal | Development | Volume | 143 |
| Issue | 23 | Pages | 4509-4520 |
| PubMed ID | 27789627 | Mgi Jnum | J:237533 |
| Mgi Id | MGI:5812860 | Doi | 10.1242/dev.139295 |
| Citation | Lian G, et al. (2016) Filamin A- and formin 2-dependent endocytosis regulates proliferation via the canonical Wnt pathway. Development 143(23):4509-4520 |
| abstractText | Actin-associated proteins regulate multiple cellular processes, including proliferation and differentiation, but the molecular mechanisms underlying these processes are unclear. Here, we report that the actin-binding protein filamin A (FlnA) physically interacts with the actin-nucleating protein formin 2 (Fmn2). Loss of FlnA and Fmn2 impairs proliferation, thereby generating multiple embryonic phenotypes, including microcephaly. FlnA interacts with the Wnt co-receptor Lrp6. Loss of FlnA and Fmn2 impairs Lrp6 endocytosis, downstream Gsk3beta activity, and beta-catenin accumulation in the nucleus. The proliferative defect in Flna and Fmn2 null neural progenitors is rescued by inhibiting Gsk3beta activity. Our findings thus reveal a novel mechanism whereby actin-associated proteins regulate proliferation by mediating the endocytosis and transportation of components in the canonical Wnt pathway. Moreover, the Fmn2-dependent signaling in this pathway parallels that seen in the non-canonical Wnt-dependent regulation of planar cell polarity through the Formin homology protein Daam. These studies provide evidence for integration of actin-associated processes in directing neuroepithelial proliferation. |
