Profilin-1 Serves as a Gatekeeper for Actin Assembly by Arp2/3-Dependent and -Independent Pathways
| Autor: | James E. Bear, Cristian Suarez, Congying Wu, Jason M. Haugh, David R. Kovar, Jonathan D. Winkelman, Jeremy D. Rotty, Elizabeth M. Haynes, Heath E. Johnson |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Fetal Proteins
Male Arp2/3 complex Formins macromolecular substances Biology Article General Biochemistry Genetics and Molecular Biology Actin-Related Protein 2-3 Complex 03 medical and health sciences Mice Profilins 0302 clinical medicine Stress Fibers Image Processing Computer-Assisted Animals Molecular Biology 030304 developmental biology Actin nucleation 0303 health sciences Microfilament Proteins Actin remodeling Ena/Vasp homology proteins Nuclear Proteins Cell Biology Fibroblasts Actin cytoskeleton Actins Cell biology Mice Inbred C57BL Actin Cytoskeleton Profilin Microscopy Fluorescence biology.protein Female MDia1 biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Developmental Cell. (1):54-67 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2014.10.026 |
| Popis: | Summary Cells contain multiple F-actin assembly pathways, including the Arp2/3 complex, formins, and Ena/VASP, which have largely been analyzed separately. They collectively generate the bulk of F-actin from a common pool of G-actin; however, the interplay and/or competition between these pathways remains poorly understood. Using fibroblast lines derived from an Arpc2 conditional knockout mouse, we established matched-pair cells with and without the Arp2/3 complex. Arpc2 −/− cells lack lamellipodia and migrate more slowly than WT cells but have F-actin levels indistinguishable from controls. Actin assembly in Arpc2 −/− cells was resistant to cytochalasin-D and was highly dependent on profilin-1 and Ena/VASP but not formins. Profilin-1 depletion in WT cells increased F-actin and Arp2/3 complex in lamellipodia. Conversely, addition of exogenous profilin-1 inhibited Arp2/3 complex actin nucleation in vitro and in vivo. Antagonism of the Arp2/3 complex by profilin-1 in cells appears to maintain actin homeostasis by balancing Arp2/3 complex-dependent and -independent actin assembly pathways. |
| Databáze: | OpenAIRE |
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