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14 results on '"Clarke, Akanni"'

10. Dynamic morphogenesis of a pioneer axon in Drosophilaand its regulation by Abl tyrosine kinase

Author

Clarke, Akanni, McQueen, Philip G., Fang, Hsiao Yu, Kannan, Ramakrishnan, Wang, Victor, McCreedy, Evan, Buckley, Tyler, Johannessen, Erika, Wincovitch, Stephen, and Giniger, Edward

Abstract

Live imaging of an axon in its native tissue shows that its growth is protrusive and occurs by stabilization of selected filopodia. Guidance signaling, however, for example, via Abl tyrosine kinase, does not control these morphological properties directly but rather controls actin distribution to determine where filopodial dynamics can occur.

Published
2020
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11. Abl signaling directs growth of a pioneer axon in Drosophilaby shaping the intrinsic fluctuations of actin

Author

Clarke, Akanni, McQueen, Philip G., Fang, Hsiao Yu, Kannan, Ramakrishnan, Wang, Victor, McCreedy, Evan, Wincovitch, Stephen, and Giniger, Edward

Abstract

Live imaging reveals that a forward bias of the stochastic actin fluctuations in the distal part of an axon drives axon extension by advancing the protrusive, filopodial domain of the growth cone. The actin mass is itself shaped by guidance signaling via Abl tyrosine kinase, which regulates growth cone length and minimizes its disorder.

Published
2020
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12. Enabled primarily controls filopodial morphology, not actin organization, in the TSM1 growth cone in Drosophila

Author

Fang, Hsiao Yu, Forghani, Rameen, Clarke, Akanni, McQueen, Philip G., Chandrasekaran, Aravind, O'Neill, Kate M., Losert, Wolfgang, Papoian, Garegin A., and Giniger, Edward

Abstract

Ena/VASP proteins are processive actin polymerases that are required throughout animal phylogeny for many morphogenetic processes, including axon growth and guidance. Here we use in vivo live imaging of morphology and actin distribution to determine the role of Ena in promoting the growth of the TSM1 axon of the Drosophilawing. Altering Ena activity causes stalling and misrouting of TSM1. Our data show that Ena has a substantial impact on filopodial morphology in this growth cone but exerts only modest effects on actin distribution. This is in contrast to the main regulator of Ena, Abl tyrosine kinase, which was shown previously to have profound effects on actin and only mild effects on TSM1 growth cone morphology. We interpret these data as suggesting that the primary role of Ena in this axon may be to link actin to morphogenetic processes of the plasma membrane, rather than for regulating actin organization itself. These data also suggest that a key role of Ena, acting downstream of Abl, may be to maintain consistent organization and reliable evolution of growth cone structure, even as Abl activity varies in response to guidance cues in the environment.

Published
2024
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13. The Abl pathway bifurcates to balance Enabled and Rac signaling in axon patterning in Drosophila.

Author

Clarke, Akanni, Shivalkar, Madhuri, Wang, Benjamin, Kotlyanskaya, Lyudmila, Kuzina, Irina, Qun Gu, Giniger, Edward, Kannan, Ramakrishnan, Jeong-Kuen Song, and Karpova, Tatiana

Subjects
*DROSOPHILA, *ABL1 gene, *PROTEIN-tyrosine kinases
Abstract

The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. Although individual components are known, the relationships among them remain unresolved. 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 the 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. [ABSTRACT FROM AUTHOR]

Published
2017
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14. The Abl pathway bifurcates to balance Enabled and Rac signaling in axon patterning in Drosophila.

Author

Kannan R, Song JK, Karpova T, Clarke A, Shivalkar M, Wang B, Kotlyanskaya L, Kuzina I, Gu Q, and Giniger E

Subjects
Animals, Animals, Genetically Modified, Body Patterning, DNA-Binding Proteins genetics, Drosophila Proteins chemistry, Drosophila Proteins genetics, Drosophila melanogaster genetics, Fluorescence Resonance Energy Transfer, Genes, Insect, Guanine Nucleotide Exchange Factors chemistry, Guanine Nucleotide Exchange Factors genetics, Guanine Nucleotide Exchange Factors metabolism, Mutation, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neurogenesis, Neurons cytology, Neurons metabolism, Phosphoproteins chemistry, Phosphoproteins genetics, Phosphoproteins metabolism, Protein Domains, Protein Serine-Threonine Kinases chemistry, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Protein-Tyrosine Kinases genetics, Signal Transduction, rac GTP-Binding Proteins genetics, Axons metabolism, DNA-Binding Proteins metabolism, Drosophila Proteins metabolism, Drosophila melanogaster embryology, Drosophila melanogaster metabolism, Protein-Tyrosine Kinases metabolism, rac GTP-Binding Proteins metabolism
Abstract

The Abl tyrosine kinase signaling network controls cell migration, epithelial organization, axon patterning and other aspects of development. Although individual components are known, the relationships among them remain unresolved. 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 the 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., (© 2017. Published by The Company of Biologists Ltd.)

Published
2017
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