Alpha 6 beta 4 integrin heterodimer is a component of hemidesmosomes.

Abstract

Antisera that recognize the a6 and (34 subunits of integrins were found by immunoelectron microscopy to localize to hemidesmosomes in the basal cells of mouse corneal epithelium. Immunoprecipitation experiments using extracts of metabolically labeled corneal epithelial cells indicate that the primary a6-subunit-containing integrin heterodimer present is a434 and not a6431. Here we extend previous studies to report that by immunofluorescence microscopy the a6 integrin subunit colocalizes with bullous pemphigoid antigen and type V1I collagen in newly forming hemidesmosomes in the developing 17-day fetal rabbit eye. Neither the composition of the anchoring filaments, which span the region between the hemidesmosomal plaque and the lamina densa of basement membrane where the globular domain of type VII collagen is located, nor the extracellular ligand of a6.84 is known. Once anchoring filament proteins are identified, it will be of interest to determine whether any bind to a484.Hemidesmosomes are cell-substrate adhesionjunctions present along the basal cell-basement membrane junction of stratified squamous epithelia (1,2). By comparison to desmosomes, biochemical characterization of the basic components of the hemidesmosome has been slow, due in part to difficulty in obtaining hemidesmosome-enriched cellular fractions. The only characterized component of the hemidesmosome is the bullous pemphigoid antigen (BPA), a 230-kDa protein present in the cytoplasmic plaque of the hemidesmosome (3-5). BPA is found within the electron-dense cytoplasmic plaque region of the hemidesmosome. The sequence of cDNA clones encoding the BPA molecule, although not entirely complete, shows no integral membrane segment (J. Stanley, personal communication). Several other monoclonal antibodies specific to hemidesmosomes have been reported, and their antigens await characterization (6, 7). Clearly, other molecules are present in both the cytoplasmic and the extracellular aspect of the hemidesmosome.The molecule(s) that traverses the cell membrane in hemidesmosomes has yet to be identified; candidates include members of the integrin superfamily of extracellular matrix receptors (8-12). The integrins are integral membrane glycoproteins that function as cell-cell and cell-substrate adhesion molecules. As a result of our studies to localize and characterize integrin subunits present in corneal epithelium, we noted that antibodies to both the a6 and (4 integrin subunits bound to the basal cell-basement membrane zone in stationary epithelia. This prompted us to determine whether the heterodimer is associated with hemidesmosomes. The present study reports that a6 and P4 integrins colocalize with BPA and type VII collagen in hemidesmosomes of developing epithelia, that both a6 and (3 antibodies bind to hemidesmosomes as shown by immunoelectron microscopy, and that both a434 and a43l heterodimers can be identified in epithelia by immunoprecipitation. MATERIALS AND METHODSTissue Preparation. For adult corneal epithelium, New Zealand White (NZW) ...

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

“…Integrin b4 is another cellular attachment receptor which forms a a6b4 heterodimer in many epithelia (Stepp et al, 1990;Sonnenberg et al, 1991) and is required for cell adhesion on basal lamina via laminins (Kajiji et al 1989;Carter et al, 1990), forming hemidesmosomes (Jones et al, 1991; A B CE, columner epithelium; S, stroma Sonnenberg et al, 1991;Dowling et al, 1996). Considering previous cell kinetic analyses that stem cells divide only rarely under normal steady-state conditions (Potten and Morris, 1988;Cotsarelis et al, 1990;Lavker et al, 1991;Loe er and Potten, 1997), our present observations lead us to propose that the p75 NGFR -expressing cells are a speci®c basal cell subset, such as precursor cells, of the regenerating human epithelial tissues (Loe er and Potten, 1997).…”

The integrin alpha 6 beta 4 is a laminin receptor.

“…In marked contrast to the aggressive interaction of clone A cells and other invasive carcinoma cells with laminin, keratinocytes, for example, require relatively long periods of time to form adhesive contacts with the basement membrane. This adhesion, which involves the formation of complex cytoskeletal structures, appears to be tightly regulated (Carter et al ., 1990;Quaranta and Jones, 1991;Sonnenberg et al ., 1991;Stepp et al, 1990) . Perhaps, this regulation involves the latent activation of the laminin binding function of a6ß4 .…”

“…One tacit assumption in many of these studies has been that the a6-dependent adhesion of cells that express a6ß4 is mediated by low levels ofa6ß1 and not a6ß4. Moreover, recent studies on a6ß4 have not addressed this laminin receptor function directly, but have focused on its function in stratified epithelial cells such as keratinocytes (Carter et al ., 1990 ;Quaranta and Jones, 1991;Sonnenberg et al, 1991;Stepp et al ., 1990) . These groups have postulated that a6ß4 may play a critical role in the assembly and maintenance ofhemidesmosomes .…”

Expression of αvβ6integrin in oral leukoplakia

“…In normal epithelium, α 6 β 4 integrin binds to laminin-5 of the anchoring filaments and serves as an integral component of the hemidesmosome (Stepp et al, 1990;Sonnenberg et al, 1991). α 2 β 1 and α 3 β 1 integrins are localized in basal epithelial cells.…”