ZFIN ID: ZDB-PUB-140712-15
DIPA family coiled-coils bind conserved isoform-specific head domain of p120-catenin family: potential roles in hydrocephalus and heterotopia
Markham, N.O., Doll, C.A., Dohn, M.R., Miller, R.K., Yu, H., Coffey, R.J., McCrea, P.D., Gamse, J.T., Reynolds, A.B.
Date: 2014
Source: Molecular biology of the cell   25(17): 2592-603 (Journal)
Registered Authors: Doll, Caleb, Gamse, Josh, Miller, Rachel K
Keywords: none
MeSH Terms:
  • Adherens Junctions/metabolism
  • Amino Acid Sequence
  • Animals
  • Cadherins/metabolism
  • Catenins/chemistry
  • Catenins/genetics
  • Catenins/metabolism
  • Catenins/physiology*
  • Cell Line, Tumor
  • Conserved Sequence
  • Dogs
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Hydrocephalus/metabolism*
  • Madin Darby Canine Kidney Cells
  • Molecular Sequence Data
  • Neural Tube Defects/genetics
  • Protein Isoforms/metabolism
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed: 25009281 Full text @ Mol. Biol. Cell
p120-catenin (p120) modulates adherens junction (AJ) dynamics by controlling the stability of classical cadherins. Among all p120 isoforms, p120-3A and p120-1A are the most prevalent. Both stabilize cadherins, but p120-3A is preferred in epithelia, while p120-1A takes precedence in neurons, fibroblasts, and macrophages. During Epithelial-to-Mesenchymal Transition (EMT), E- to N-cadherin switching coincides with p120-3A to -1A alternative splicing. These isoforms differ by a 101 amino acid "head domain" comprising the p120-1A N-terminus. Although its exact role is unknown, the head domain likely mediates developmental and cancer-associated events linked to p120-1A expression (e.g., motility, invasion, metastasis). Here, we have identified (Delta-Interacting Protein A) DIPA as the first head domain-specific binding partner and candidate mediator of isoform 1A activity. DIPA colocalizes with AJs in a p120-1A- but not 3A-dependent manner. Moreover, all DIPA family members (DIPA, Ccdc85a, and Ccdc85c) interact reciprocally with p120 family members (p120, δ-catenin, p0071, and ARVCF), suggesting significant functional overlap. During zebrafish neural tube development, both knockdown and overexpression of DIPA phenocopy N-cadherin mutations, an effect bearing functional ties to a reported mouse hydrocephalus phenotype associated with Ccdc85c. These studies identify a novel, highly conserved interaction between two protein families that may participate either individually or collectively in N-cadherin-mediated development.