Colocalization of multiple laminin isoforms predominantly beneath hemidesmosomes in the upper lamina densa of the epidermal basement membrane

Abstract

Multiple laminin isoforms including laminins 5 (α3 β3 γ2), 6 (α3 β1 γ1), 10 (α5 β1 γ1), and possibly laminins 7 (α3 β2 γ1) and 11 (α5 β2 γ1) are present in the epidermal basement membrane. However, only the precise epidermal ultrastructural localization of laminin 5 (α3 β3 γ2) has been elucidated. We therefore determined the precise expression and ultrastructural localization of the α5, β1, β2, and γ1 chains in the epidermis. The expression of laminin chains in skin samples was analyzed from patients with epidermolysis bullosa (EB, n = 15) that harbor defects in specific hemidesmosome (HD)-associated components. The expression of the α5, β1, and γ1 chains (present in laminins 10/11) and β2 chain (laminins 7/11) was unaffected in all intact (unseparated) skin of EB patients including Herlitz junctional EB with laminin-5 defects (n=6). In the basement membrane of human epidermis, the α5, β1, β2, and γ1 chains were expressed but also localized to the dermal vessels. Immunogold electron microscopy of normal human epidermis localized the α5, β1, β2, and γ1 chains to the upper lamina densa, with between 84% and 92% of labeling restricted to beneath the HDs, similar to laminin 5 (n≥200 gold particles per sample, sample number n=4) but distinct from collagen IV labeling (with only 63% labeling beneath HDs, p<0.001). Taken together, the majority of the α5β1/β2γ1 laminin chains are located beneath HDs. This suggests that laminin-10-associated chains have specific functions or molecular interactions beneath HDs in the epidermal basement membrane. © The Histochemical Society, Inc.