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PreprintCited by 4Developmental Biology and Gene RegulationHippo pathway signaling and YAP/TAZAxon Guidance and Neuronal Signaling

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Contributions of the Dachsous intracellular domain to Dachsous-Fat signaling

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Tripathi, Bipin Kumar, Irvine, Kenneth D.·2024·Development
DOI 10.1101/2024.04.03.587940PMC PMC11634027

Preprint — published as 10.1242/dev.202919 · Paper page

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Abstract

The protocadherins Fat and Dachsous regulate organ growth, shape, patterning, and planar cell polarity. Although Dachsous and Fat have been described as ligand and receptor, respectively, in a signal transduction pathway, there is also evidence for bidirectional signaling. Here we assess signaling downstream of Dachsous through analysis of its intracellular domain. Genomic deletions of conserved sequences within dachsous identified regions of the intracellular domain required for normal development. Deletion of the A motif increased Dachsous protein levels and decreased wing size. Deletion of the D motif decreased Dachsous levels at cell membranes, increased wing size, and disrupted wing, leg and hindgut patterning and planar cell polarity. Co-immunoprecipitation experiments established that the D motif is necessary and sufficient for association of Dachsous with four key partners: Lowfat, Dachs, Spiny-legs, and MyoID. Subdivision of the D motif identified distinct regions that are preferentially responsible for association with Lft versus Dachs. Our results identify motifs that are essential for Dachsous function and are consistent with the hypothesis that the key function of Dachsous is regulation of Fat.

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Metadata

Authors
Tripathi, B. K., & Irvine, K. D.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Irvine, Kenneth D.
ORCID
Venue
Development
Publisher
openRxiv
Published
2024-04-03
Volume
151
Issue
23
ISSN
0950-1991 (ISSN-L)
DOI
10.1101/2024.04.03.587940
PMC
PMC11634027
OpenAlex
W4404112806
Cited by
4
References
1
Citations by year
2026: 2 · 2025: 2
FWCI
0.54
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Development (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • Rutgers, The State University of New Jersey
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35GM131748)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
Dachsous, fats, protocadherins, cytoplasmic domain, planar cell polarity, wing patterning, organ growth, DACH, bidirectional signaling, Drosophila

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