Expression of the integrin alpha 6 beta 4 in peripheral nerves: localization in Schwann and perineural cells and different variants of the beta 4 subunit.
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.
Niessen
C M
CM
The Netherlands Cancer Institute, Division of Cell Biology, Amsterdam.
Cremona
O
O
Daams
H
H
Ferraresi
S
S
Sonnenberg
A
A
Marchisio
P C
PC
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D039161:Integrin alpha6beta4; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism / Q000648:ultrastructure
D000954:Antigens, Surface; D017931:DNA Primers; D039161:Integrin alpha6beta4; D016023:Integrins