title: Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required for vertebrate gastrulation.
abstract: Non-canonical Wnt signaling plays important roles during vertebrate embryogenesis and is required for cell motility during gastrulation. However, the molecular mechanisms of how Wnt signaling regulates modification of the actin cytoskeleton remain incompletely understood. We had previously identified the Formin homology protein Daam1 as an important link between Dishevelled and the Rho GTPase for cytoskeletal modulation. Here, we report that Profilin1 is an effector downstream of Daam1 required for cytoskeletal changes. Profilin1 interacted with the FH1 domain of Daam1 and was localized with Daam1 to actin stress fibers in response to Wnt signaling in mammalian cells. In addition, depletion of Profilin1 inhibited stress fiber formation induced by non-canonical Wnt signaling. Inhibition or depletion of Profilin1 in vivo specifically inhibited blastopore closure in Xenopus but did not affect convergent extension movements, tissue separation or neural fold closure. Our studies define a molecular pathway downstream of Daam1 that controls Wnt-mediated cytoskeletal reorganization for a specific morphogenetic process during vertebrate gastrulation.
authors.affiliation: Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson School of Medicine, Piscataway, NJ 08854, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Khadka
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Ritu
authors.initials: R
authors.lastname: Bharti
authors.forename: Loren W
authors.initials: LW
authors.lastname: Runnels
authors.forename: Igor B
authors.initials: IB
authors.lastname: Dawid
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D017077:Culture Media, Conditioned; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D005775:Gastrula / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D008840:Microfilament Proteins; D009024:Morphogenesis; D051304:Profilins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D022502:Stress Fibers / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017077:Culture Media, Conditioned; C499094:DAAM1 protein, human; D008840:Microfilament Proteins; C495740:Pfn1 protein, rat; D051304:Profilins; D051153:Wnt Proteins; D020741:rho GTP-Binding Proteins