Corrigendum

Signal transduction by the α6β4 integrin: distinct β4 subunit sites mediate recruitment of Shc/Grb2 and association with the cytoskeleton of hemidesmosomes. Mainiero F., Pepe A., Wary K.K., Spinardi L., Mohammadi M., Schlessinger J., Giancotti F.G. The EMBO Journal. 1995;14:4470–4481. doi: 10.1002/j.1460-2075.1995.tb00126.x.

The α₆β₄ integrin is a major receptor for the basement membrane component laminin 5. Ligation of the α₆β₄ integrin induces tyrosine phosphorylation of the β₄ cyto plasmic domain, followed by recruitement of the adaptor protein Shc and activation of mitogen-activated protein (MAP) kinase cascades (Mainiero et al., 1995, 1997). In addition to its signaling function, the cytoplasmic domain of β₄ plays a crucial role in the assembly of hemidesmosomes (Spinardi et al., 1993; Murgia et al., 1998). Previous results from our laboratory had suggested that the β₄ cytoplasmic domain residues Y1422 and Y1440 (which resemble a tyrosine-based activation motif or TAM) were required for incorporation of recombinant β₄ into hemidesmosome-like adhesions of 804G cells in culture (Mainiero et al., 1995). Recent studies have, however, indicated that residues C-terminal to residue 1355 in the β₄ cytoplasmic domain are not necessary for the formation of hemidesmosome-like adhesions by both cultured 804G cells and keratinocytes (Niessen et al., 1997; Schaapveld et al., 1998). To clarify the origin of this discrepancy, we have performed a number of experiments. An analysis of the entire coding sequence of the constructs used in our previous study has revealed that the Y1422F and the Y1440F mutations (Mainiero et al., 1995) were introduced in a version of β₄ that contained a 24 bp in-frame deletion of the sequences encoding amino acids 941–948 (QDHTIVDT). Interestingly, this sequence is located in the membrane-proximal portion of the cytoplasmic domain of β₄, which previous studies had indicated to be dispensable for incorporation in hemidesmosome-like adhesions (Spinardi et al., 1993) and had therefore not been covered by our initial sequence re-analysis. The nature and origin of the variant cDNA lacking amino acids 941–948 remain to be established. We have observed that this deletion in combination with the Y1422/1440F mutation (referred to as YZ or TAM mutant in Mainiero et al., 1995) prevents incorporation of β₄ into hemidesmosomes in 804G cells, in agreement with our original result. However, the introduction of the Y1422/1440F mutation in the canonical form A of β₄ does not prevent incorporation in hemidesmosome-like adhesions in 804G cells, as shown previously by others (Niessen et al., 1997; Schaapveld et al., 1998). The synergy between the TAM mutation and the deletion 941–948 suggests that Y1422 and Y1440 may play a role in assembly of hemidesmosomes. However, a full assessment of this role may require examination of the assembly of ‘bona fide’ hemidesmosomes in skin organ culture systems or in vivo. Some of the conclusions in Mainiero et al. (1995) must be re-evaluated in light of these new observations.

Pamela Blaikie, Michael Dans, Laurent Gagnoux-Palacios and Filippo G.Giancotti