Published 29 September 2003. doi:10.1083/jcb.200307089
© The Rockefeller University Press,
0021-9525/2003/9/1305 $5.00
The Journal of Cell Biology, Volume 162, Number 7, 1305-1315
Maintaining epithelial integrity
:
a function for gigantic spectraplakin isoforms in adherens junctions
Katja Röper and
Nicholas H. Brown
Wellcome Trust/Cancer Research UK Institute and Department of Anatomy, University of Cambridge, Cambridge, CB2 1QR UK
Address correspondence to Nicholas H. Brown, Wellcome Trust/Cancer Research UK Institute and Dept. of Anatomy, University of Cambridge, Tennis Court Rd., Cambridge, CB2 1QR UK. Tel.: 44-1223-334128. Fax: 44-1223-334089. email: n.brown{at}welc.cam.ac.uk
The Short stop (Shot/Kakapo) spectraplakin is a giant cytoskeletal protein, which exists in multiple isoforms with characteristics of both spectrin and plakin superfamilies. Previously characterized Shot isoforms are similar to spectrin and dystrophin, with an actin-binding domain followed by spectrin repeats. We describe a new large exon within the shot locus, which encodes a series of plakin repeats similar to the COOH terminus of plakins such as plectin and BPAG1e. We find that the plakin repeats are inserted between the actin-binding domain and spectrin repeats, generating isoforms as large as 8,846 residues, which could span 400 nm. These novel isoforms localized to adherens junctions of embryonic and follicular epithelia. Loss of Shot within the follicle epithelium leads to double layering and accumulation of actin and ZO-1 in between, and a reduction of Armadillo and Discs lost within, mutant cells, indicative of a disruption of adherens junction integrity. Thus, we identify a new role for spectraplakins in mediating cellcell adhesion.
Key Words: actin; cytoskeleton; cell junctions; adhesion; follicle epithelium
Abbreviations used in this paper: ABD, actin-binding domain; dlt, Discs lost; FasIII, Fasciclin III; IP, immunoprecipitation; PY, phosphotyrosine; WB, Western blot.

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