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First published online 4 December 2002
doi: 10.1242/jcs.00241
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Research Article |
6ß4 important for hemidesmosome assembly
1 The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121,
1066 CX Amsterdam, The Netherlands
2 University Hospital Geneva, Department of Dermatology, CH-1211 Geneva,
Switzerland
* Present address: Department of Human Genetics, Academic Medical Center,
University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam
Author for correspondence (e-mail:
a.sonnenberg{at}nki.nl)
Accepted 28 October 2002
Hemidesmosomes (HDs) are multi-protein complexes that promote stable adhesion of epithelial cells to the underlying extracellular matrix. We assessed the interactions between different hemidesmosomal components with each other, mapped the binding sites and studied the importance of these interactions for HD assembly in yeast two-hybrid and cell-transfection assays. The results show that: (1) bullous pemphigoid antigen (BP) 180 binds not only to BP230, but also to plectin. The interactions between these proteins are facilitated by the Y subdomain in the N-terminal plakin domain of BP230 and plectin, and residues 145-230 of the cytoplasmic domain of BP180; (2) different, but overlapping, sequences on BP180 mediate binding to ß4, which, in turn associates with BP180 via its third fibronectin type III repeat; (3) sequences in the N-terminal extremity of BP230 mediate its binding to ß4, which requires the C-terminal end of the connecting segment up to the fourth FNIII repeat of the ß4 subunit. (4) Finally, cell-transfection studies showed that the localization of BP230 into hemidesmosome-like structures depends on its Z-Y subdomains as well as on the availability of BP180. By having further uncovered interactions between various hemidesmosomal components, mapped the involved binding sites and dissected a hierarchy of interactions relevant for their topogenic fate, our findings give novel insights into the molecular organization of hemidesmosomes.
Key words: Hemidesmosome, Integrin, Bullous pemphigoid, Plakin, Keratinocyte
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