The Abl pathway bifurcates to balance Enabled and Rac signaling in axon patterning in Drosophila
| Autor: | Edward Giniger, Akanni Clarke, Tatiana S. Karpova, Madhuri Shivalkar, Benjamin Wang, Ramakrishnan Kannan, Lyudmila Kotlyanskaya, Irina Kuzina, Jeong-Kuen Song, Qun Gu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neurogenesis Genes Insect Nerve Tissue Proteins Biology Protein Serine-Threonine Kinases Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Protein Domains hemic and lymphatic diseases medicine Fluorescence Resonance Energy Transfer Animals Drosophila Proteins Guanine Nucleotide Exchange Factors Spectrin Axon Kinase activity Molecular Biology Actin Body Patterning Neurons ABL Signal transducing adaptor protein Cell migration Cell Biology Protein-Tyrosine Kinases Phosphoproteins Protein subcellular localization prediction Axons Cell biology rac GTP-Binding Proteins DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Drosophila melanogaster Mutation Axon guidance 030217 neurology & neurosurgery Developmental Biology Signal Transduction Research Article |
| Zdroj: | Development (Cambridge, England). 144(3) |
| ISSN: | 1477-9129 |
| Popis: | The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. While individual components are known, the relationships among them remain mysterious. We now use FRET measurements of pathway activity, analysis of protein localization and genetic epistasis to dissect the structure of this network in Drosophila. We find that the adaptor protein Disabled stimulates Abl kinase activity. Abl suppresses the actin regulatory factor Enabled, and we find that Abl also acts through the GEF Trio to stimulate the signaling activity of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intramolecular repression of Trio GEF activity by the Trio N-terminal domain. Finally, we show that a key target of Abl signaling in axons is the WAVE complex that promotes formation of branched actin networks. Thus, we show that Abl constitutes a bifurcating network, suppressing Ena activity in parallel with stimulation of WAVE. We suggest that the balancing of linear and branched actin networks by Abl is likely to be central to its regulation of axon patterning. |
| Databáze: | OpenAIRE |
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