The Dilute domain in Canoe is not essential for linking cell junctions to the cytoskeleton but supports morphogenesis robustness

McParland, Emily D.; Butcher, T. Amber; Gurley, Noah J.; Johnson, Ruth I.; Slep, Kevin C.; Peifer, Mark

doi:10.1242/jcs.261734

Cited by 3 publications

References 47 publications

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The dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

McParland,

Gurley,

Wolfsberg

et al. 2024

Preprint

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During embryonic development and adult homeostasis epithelial cells must change shape and move without disrupting the tissue’s dynamic architecture. This requires robust linkage of cell-cell adherens junctions to the force-generating actomyosin cytoskeleton. Drosophila Canoe and mammalian Afadin play key roles in this linkage. One central task for the field is defining how upstream inputs from Ras-family GTPases regulate Canoe and Afadin. They are unusual in that they share two tandem Ras-association (RA) domains, which, when deleted, virtually eliminate Canoe function. Previous work in vitro suggested RA1 and RA2 differ in their ability to bind GTPases, but their individual functions in vivo remain unknown. Combining bioinformatic and biochemical approaches, we find that both RA1 and RA2 bind to active Rap1 with similar affinities, and that conserved N-terminal extensions play a role in binding. We created Drosophilacanoemutants to test RA1 and RA2 function in vivo. Despite their similar affinities for Rap1, RA1 and RA2 play strikingly different roles. Deleting RA1 virtually eliminates Canoe function in morphogenesis, while mutants lacking RA2 are viable and fertile but have defects in junctional reinforcement in embryos and during pupal eye development. These data significantly expand our understanding of how adherens junction:cytoskeletal linkage is regulated.

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The dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

McParland,

Gurley,

Wolfsberg

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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First person – Emily D. McParland and T. Amber Butcher

2024

Journal of Cell Science

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First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Emily D. McParland and T. Amber Butcher are co-first authors on ‘ The Dilute domain in Canoe is not essential for linking cell junctions to the cytoskeleton but supports morphogenesis robustness’, published in JCS. Emily and Amber conducted the research described in this article while they were postbaccalaureate research assistants in the labs of Dr Mark Peifer (E.D.M. and T.A.B.) and Dr Kevin Slep (T.A.B.) at Chapel Hill Department of Biology, University of North Carolina, USA. Emily is now a PhD student in the lab of Dr Thomas Roberts at Brown University, Providence, USA, where she is broadly interested in functional morphology and muscle biomechanics, and focuses on the function of the collagenous extracellular matrix in muscle force production. Amber is a PhD student in the lab of Dr Eric Greene at Columbia University Department of Biochemistry and Molecular Biophysics, New York, USA, where she uses biochemical and biophysical techniques to investigate protein function, most recently within the context of homologous recombination.

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The dual Ras-association domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

McParland,

Gurley,

Wolfsberg

et al. 2024

Journal of Cell Science

View full text Add to dashboard Cite

During development cells must change shape and move without disrupting dynamic tissue architecture. This requires robust linkage of cell-cell adherens junctions to the force-generating actomyosin cytoskeleton. Drosophila Canoe and mammalian Afadin play key roles. One central task for the field is defining mechanisms by which upstream inputs from Ras-family GTPases regulate Canoe/Afadin. They are unusual in sharing two tandem Ras-association (RA) domains, which, when deleted, virtually eliminate Canoe function. Work in vitro suggested RA1 and RA2 differ in GTPase affinity, but their individual functions in vivo remain unknown. Combining bioinformatic and biochemical approaches, we find that both RA1 and RA2 bind to active Rap1 with similar affinities, and their conserved N-terminal extensions enhance binding. We created Drosophila canoe mutants to test RA1 and RA2 function in vivo. Despite their similar affinities for Rap1, RA1 and RA2 play strikingly different roles. Deleting RA1 virtually eliminates Canoe function, while mutants lacking RA2 are viable and fertile but have defects in junctional reinforcement in embryos and during pupal eye development. These data significantly expand our understanding of regulation of adherens junction:cytoskeletal linkage.

show abstract

The Dilute domain in Canoe is not essential for linking cell junctions to the cytoskeleton but supports morphogenesis robustness

Cited by 3 publications

References 47 publications

The dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

The dual Ras Association (RA) Domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

First person – Emily D. McParland and T. Amber Butcher

The dual Ras-association domains of Drosophila Canoe have differential roles in linking cell junctions to the cytoskeleton during morphogenesis

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