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Molecular and Cellular Biology, September 2006, p. 6598-6608, Vol. 26, No. 17
0270-7306/06/$08.00+0     doi:10.1128/MCB.00241-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Variable Transmembrane Domain of Drosophila N-Cadherin Regulates Adhesive Activity{dagger}

Shinichi Yonekura,1,{ddagger} Chun-Yuan Ting,1,{ddagger} Guilherme Neves,2 Kimberly Hung,1 Shu-ning Hsu,3 Akira Chiba,3 Andrew Chess,2 and Chi-Hon Lee1*

Unit on Neuronal Connectivity, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892,1 Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114,2 Department of Cell and Structure Biology, University of Illinois, Urbana, Illinois 618013

Received 8 February 2006/ Returned for modification 27 March 2006/ Accepted 16 June 2006

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.

* Corresponding author. Mailing address: Unit of Neuronal Connectivity, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Building 18T, Room 106, MSC 5431, Bethesda, MD 20892. Phone: (301) 435-1940. Fax: (301) 496-4491. E-mail: leechih{at}mail.nih.gov.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

Molecular and Cellular Biology, September 2006, p. 6598-6608, Vol. 26, No. 17
0270-7306/06/$08.00+0     doi:10.1128/MCB.00241-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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