Expression of the integrin α6β4 in peripheral nerves: localization in schwann and perineural cells and different variants of the β4 subunit

Abstract

Integrin alpha 6 beta 4 is expressed in human peripheral nerves, but not in the central nervous system. This integrin heterodimer has previously been found in perineural fibroblast-like cells and in Schwann cells (SCs), which both assemble a basement membrane but do not form hemidesmosomes. We show here that in SCs, which had formed a myelin sheath, alpha 6 beta 4 was enriched in the proximity of the nucleus, at Ranvier paranodal areas and at Schmitt-Lanterman clefts; alpha 6 beta 4 was also found at the grooved interface between small axons and non-myelinating SCs. Immunoprecipitation of human peripheral nerves, in combination with Western blotting showed that beta 4 is associated with the alpha 6A subunit. Northern blot analysis of human peripheral nerves showed a single beta 4 transcript of 6 kb. Using the reverse transcriptase polymerase chain reaction, we detected two mRNA species, one for the most common (−70, -53) form of beta 4 and the other encoding the (+53) variant of beta 4. Cultured SCs were devoid of alpha 6 beta 4 but expressed alpha 6 beta 1, indicating that SCs lose beta 4 expression when contact with neurons is lost. Thus, resting SCs in contact with axons express alpha 6A in combination with beta 4, irrespective of myelin formation. We suggest that alpha 6 beta 4 expressed in SCs plays a role in peripheral neurogenesis.

Differential cell composition and split epidermal differentiation in human palm, sole, and hip skin

“…The final cluster, fibroblast IV, is marked by expression of ANGPTL7 and C2orf40 , matching a minor, specialized population of fibroblasts, 14 referred to as C4, 32 the function of which has not been previously determined. This population is also defined by exclusive expression of ITGA6 and ITGB4 , which have been shown to be expressed specifically in Schwann cells and perineural fibroblasts in the dermis, 53 as well as CLDN1 and SLC2A , both of which are currently used as markers for perineural cells. 54 , 55 Considering the increased innervation in the palmar skin compared with the rest of the body, 56 this perineural role would match with the increased proportion of fibroblast IV cells seen in the palm, where it makes up 14% rather than <8% in the other two sites ( Figure 3 ).…”

Junctional epithelium and hemidesmosomes: Tape and rivets for solving the “percutaneous device dilemma” in dental and other permanent implants

“…Integrin α6β4, despite its role in epithelial HD formation, has been reportedly expressed in non-epithelial cells such as neurons [ 120 ], astrocytes [ 121 ], Schwann cells [ 122 ], and endothelial cells that all lack HDs [ 123 ]. The role α6β4 plays in such cells is diverse, and in many cases controversial, but there is agreement that α6β4 broadly regulates migration and motility [ 124 ].…”

Integrin α6: a potential target for cancer molecular imaging and targeting therapy

“…In tumors, the expression and function of integrins are abnormal, which promotes tumor development, angiogenesis, invasion, metastasis, and immune escape and causes tumor tolerance to radiotherapy and chemotherapy [11][12][13]. The integrin α6 subunit is CD49f, which can form α6β1 or α6β4 integrins with the integrin β1 subunit (CD29) and integrin β4 subunit (CD104), and the ligand of α6β1 and α6β4 is laminin [14][15][16][17][18][19]. Integrin α6 is significantly overexpressed in a variety of cancers, including hepatocellular carcinoma (HCC), pancreatic cancer, colorectal adenocarcinoma, head and neck squamous cell carcinoma, acute myeloid leukemia, breast cancer, lung squamous cell carcinoma, esophageal squamous cell carcinoma, and other cancers, and abnormally high expression has been associated with lower survival rates and poorer prognosis [20][21][22].…”