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© The Rockefeller University Press, 0021-9525/2000//969 $5.00
The Journal of Cell Biology, Volume 149, Number 4, , 2000 969-982

The Tetraspan Molecule Cd151, a Novel Constituent of Hemidesmosomes, Associates with the Integrin 6β4 and May Regulate the Spatial Organization of Hemidesmosomes

^a Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
^b Division of Biophysics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.(31) 20-5121944(31) 20-5121942

asonn{at}nki.nl

CD151 is a cell surface protein that belongs to the tetraspan superfamily. It associates with other tetraspan molecules and certain integrins to form large complexes at the cell surface. CD151 is expressed by a variety of epithelia and mesenchymal cells. We demonstrate here that in human skin CD151 is codistributed with 3β1 and 6β4 at the basolateral surface of basal keratinocytes. Immunoelectron microscopy showed that CD151 is concentrated in hemidesmosomes. By immunoprecipitation from transfected K562 cells, we established that CD151 associates with 3β1 and 6β4. In β4-deficient pyloric atresia associated with junctional epidermolysis bullosa (PA-JEB) keratinocytes, CD151 and 3β1 are clustered together at the basal cell surface in association with patches of laminin-5. Focal adhesions are present at the periphery of these clusters, connected with actin filaments, and they contain both CD151 and 3β1. Transient transfection studies of PA-JEB cells with β4 revealed that the integrin 6β4 becomes incorporated into the 3β1-CD151 clusters where it induces the formation of hemidesmosomes. As a result, the amount of 3β1 in the clusters diminishes and the protein becomes restricted to the peripheral focal adhesions. Furthermore, CD151 becomes predominantly associated with 6β4 in hemidesmosomes, whereas its codistribution with 3β1 in focal adhesions becomes partial. The localization of 6β4 in the pre-hemidesmosomal clusters is accompanied by a strong upregulation of CD151, which is at least partly due to increased cell surface expression. Using β4 chimeras containing the extracellular and transmembrane domain of the IL-2 receptor and the cytoplasmic domain of β4, we found that for recruitment of CD151 into hemidesmosomes, the β4 subunit must be associated with 6, confirming that integrins associate with tetraspans via their subunits. CD151 is the only tetraspan identified in hemidesmosomal structures. Others, such as CD9 and CD81, remain diffusely distributed at the cell surface.

In conclusion, we show that CD151 is a major component of (pre)-hemidesmosomal structures and that its recruitment into hemidesmosomes is regulated by the integrin 6β4. We suggest that CD151 plays a role in the formation and stability of hemidesmosomes by providing a framework for the spatial organization of the different hemidesmosomal components.

Key Words: integrin 6β4 • tetraspan CD151 • hemidesmosome • focal adhesion • cross-talk

© 2000 The Rockefeller University Press

Abbreviations used in this paper: BP180, bullous pemphigoid antigen 180; BP230, bullous pemphigoid antigen 230; IL2R, interleukin-2 receptor; PA-JEB, pyloric atresia associated with junctional epidermolysis bullosa.

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