HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Hokkaido University Hospital >
Peer-reviewed Journal Articles, etc >

Extracellular cleavage of collagen XVII is essential for correct cutaneous basement membrane formation

Files in This Item:
HumMolGenet25_328.pdf1.6 MBPDFView/Open
SupplementaryFigures_HMG-2015-TWB-00765R1Nishimura.pdfSupplementary material398.64 kBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/63665

Title: Extracellular cleavage of collagen XVII is essential for correct cutaneous basement membrane formation
Authors: Nishimura, Machiko Browse this author
Nishie, Wataru Browse this author →KAKEN DB
Shirafuji, Yoshinori Browse this author →KAKEN DB
Shinkuma, Satoru Browse this author →KAKEN DB
Natsuga, Ken Browse this author →KAKEN DB
Nakamura, Hideki Browse this author →KAKEN DB
Sawamura, Daisuke Browse this author →KAKEN DB
Iwatsuki, Keiji Browse this author →KAKEN DB
Shimizu, Hiroshi Browse this author →KAKEN DB
Issue Date: 15-Jan-2016
Publisher: Oxford University Press
Journal Title: Human molecular genetics
Volume: 25
Issue: 2
Start Page: 328
End Page: 339
Publisher DOI: 10.1093/hmg/ddv478
PMID: 26604146
Abstract: In skin, basal keratinocytes in the epidermis are tightly attached to the underlying dermis by the basement membrane (BM). The correct expression of hemidesmosomal and extracellular matrix (ECM) proteins is essential for BM formation, and the null-expression of one molecule may induce blistering diseases associated with immature BM formation in humans. However, little is known about the significance of post-translational processing of hemidesmosomal or ECM proteins in BM formation. Here we show that the C-terminal cleavage of hemidesmosomal transmembrane collagen XVII (COL17) is essential for correct BM formation. The homozygous p.R1303Q mutation in COL17 induces BM duplication and blistering in humans. Although laminin 332, a major ECM protein, interacts with COL17 around p.R1303, the mutation leaves the binding of both molecules unchanged. Instead, the mutation hampers the physiological C-terminal cleavage of COL17 in the ECM. Consequently, non-cleaved COL17 ectodomain remnants induce the aberrant deposition of laminin 332 in the ECM, which is thought to be the major pathogenesis of the BM duplication that results from this mutation. As an example of impaired cleavage of COL17, this study shows that regulated processing of hemidesmosomal proteins is essential for correct BM organization in skin.
Rights: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Hum. Mol. Genet. (2016) 25 (2): 328-339. is available online at: http://hmg.oxfordjournals.org/content/25/2/328
Type: article (author version)
URI: http://hdl.handle.net/2115/63665
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 西村 真智子

Export metadata:

OAI-PMH ( junii2 , jpcoar )


 

Feedback - Hokkaido University