The variable transmembrane domain of Drosophila N-cadherin regulates adhesive activity

Shinichi Yonekura, Chun Yuan Ting, Guilherme Neves, Kimberly Hung, Shu Ning Hsu, Akira Chiba, Andrew Chess, Chi Hon Lee

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Drosophila N-cadherin (CadN) is an evolutionarily conserved classic cadherin which has a large, complex extracellular domain and a catenin-binding cytoplasmic domain. The CadN locus contains three modules of alternative exons (7a/b, 13a/b, and 18a/b) and undergoes alternative splicing to generate multiple isoforms. Using quantitative transcript analyses and green fluorescent protein-based cell sorting, we found that during development CadN alternative splicing is regulated in a temporal but not cell-type-specific fashion. In particular, exon 18b is predominantly expressed during early developmental stages, while exon 18a is prevalent at the late developmental and adult stages. All CadN isoforms share the same molecular architecture but have different sequences in their extracellular and transmembrane domains, suggesting functional diversity. In vitro quantitative cell aggregation assays revealed that all CadN isoforms mediate homophilic interactions, but the isoforms encoded by exon 18b have a higher adhesive activity than those by its alternative, 18a. Domain-swapping experiments further revealed that the different sequences in the transmembrane domains of isoforms are responsible for their differential adhesive activities. CadN alternative splicing might provide a novel mechanism to fine-tune its adhesive activity at different developmental stages or to restrict the use of high-affinity 18b-type isoforms at the adult stage.

Original languageEnglish (US)
Pages (from-to)6598-6608
Number of pages11
JournalMolecular and cellular biology
Volume26
Issue number17
DOIs
StatePublished - Sep 1 2006

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yonekura, S., Ting, C. Y., Neves, G., Hung, K., Hsu, S. N., Chiba, A., Chess, A., & Lee, C. H. (2006). The variable transmembrane domain of Drosophila N-cadherin regulates adhesive activity. Molecular and cellular biology, 26(17), 6598-6608. https://doi.org/10.1128/MCB.00241-06