Defining redundancy in the stickers and spacers of the cell-cell junction protein Canoe's intrinsically disordered region
- 1University of North Carolina
Abstract
Cell-cell adherens junctions (AJs) and their dynamic cytoskeletal linkage power morphogenesis. AJs are enormous complexes with hundreds of proteins linked by multivalent interactions. Like other biomolecular condensates, intrinsically disordered regions (IDRs) in junctional proteins play important roles in AJ assembly and function, using spacer elements to span distances, and stickers to engage targets. To define molecular mechanisms, we need to define the functional units within IDRs. Drosophila Canoe, homolog of human Afadin, is our model. Canoe mediates morphogenesis and has an extensive IDR, with two conserved F-actin-binding stickers and two poorly conserved spacers. We combined biochemical, genetic and cell biological approaches to define the function of these IDR elements. While no single element is essential, deleting the full IDR essentially eliminates Canoe function. By scrambling the amino acid sequence of the spacers, we find that length and composition are more important than amino acid sequences, though sequences in the C-terminal spacer affect Canoe localization. Finally, we test redundancy of the F-actin-binding stickers. Deleting both reduces but does not eliminate viability, and sensitized assays reveal their redundant roles. These data reveal the robustness of IDRs.
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BibTeX
@misc{wiltshire2026defining,
title = {{Defining redundancy in the stickers and spacers of the cell-cell junction protein Canoe's intrinsically disordered region}},
author = {R. Wiltshire and K. C. Slep and J. Lamb and S. E. Clark and M. Peifer and C. C. Jensen},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.754968},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.754968v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Defining redundancy in the stickers and spacers of the cell-cell junction protein Canoe's intrinsically disordered region
AU - R. Wiltshire
AU - K. C. Slep
AU - J. Lamb
AU - S. E. Clark
AU - M. Peifer
AU - C. C. Jensen
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.754968
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.754968v1
AB - Cell-cell adherens junctions (AJs) and their dynamic cytoskeletal linkage power morphogenesis. AJs are enormous complexes with hundreds of proteins linked by multivalent interactions. Like other biomolecular condensates, intrinsically disordered regions (IDRs) in junctional proteins play important roles in AJ assembly and function, using spacer elements to span distances, and stickers to engage targets. To define molecular mechanisms, we need to define the functional units within IDRs. Drosophila Canoe, homolog of human Afadin, is our model. Canoe mediates morphogenesis and has an extensive IDR, with two conserved F-actin-binding stickers and two poorly conserved spacers. We combined biochemical, genetic and cell biological approaches to define the function of these IDR elements. While no single element is essential, deleting the full IDR essentially eliminates Canoe function. By scrambling the amino acid sequence of the spacers, we find that length and composition are more important than amino acid sequences, though sequences in the C-terminal spacer affect Canoe localization. Finally, we test redundancy of the F-actin-binding stickers. Deleting both reduces but does not eliminate viability, and sensitized assays reveal their redundant roles. These data reveal the robustness of IDRs.
ER -