Tiina Hurskainen | PubMed Health

PubMed2006

Collagen XVII is expressed in human CNS neurons.

Type XVII collagen (collagen XVII) is a component of hemidesmosomes, which connect epithelial cells to the underlying basement membrane. Previously, an association has been suggested between neurological disorders and the skin disease bullous pemphigoid, where autoimmunity is directed against collagen XVII. Furthermore, the lack of alpha6 integrin, a ligand of collagen XVII, has been implicated in defects of cortical organization in the mouse brain. In this study, we demonstrate for the first time the presence of collagen XVII in neurons of the human brain by in situ hybridisation, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). We propose that collagen XVII may be involved in the pathogenesis of various disorders affecting neuronal migration or synaptic plasticity.

Adult↗

PubMed2005

Molecular mechanisms of junctional epidermolysis bullosa: Col 15 domain mutations decrease the thermal stability of collagen XVII.

Mutations in the collagen XVII gene, COL17A1, are associated with junctional epidermolysis bullosa. Most COL17A1 mutations lead to a premature termination codon (PTC), whereas only a few mutations result in amino acid substitutions or deletions. We describe here two novel glycine substitutions, G609D and G612R, and a splice site mutation resulting in a deletion of three Gly-X-Y amino acid triplets. In order to investigate the molecular pathomechanisms of non-PTC mutations, G609D and G612R and two previously known substitutions, G627V and G633, and deletion of the amino acids 779-787 were introduced into recombinant collagen XVII. The thermal stability of the mutated collagens was assessed using trypsin digestions at incremental temperatures. All the four glycine substitutions significantly destabilized the ectodomain of collagen XVII, which manifested as 16 degrees C-20 degrees C lower T(m) (midpoint of the helix-to-coil transition). These results were supported by secondary structure predictions, which suggested interruptions of the collagenous triple helix within the largest collagenous domain, Col15. In contrast, deletion of the three full Gly-X-Y triplets, amino acids 779-787, had no overall effect on the stability of the ectodomain, as the deletion was in register with the triplet structure and also generated compensatory changes in the NC15 domain.

Adult↗