Biology Reference
In-Depth Information
Chapter 3
Cooperation Between Proteolysis
and Endocytosis in Collagen Turnover
Thomas H. Bugge and Niels Behrendt
Abstract Studies conducted as of today collectively suggest that the degradation of
collagen in mammals is carried out in equal parts within the extracellular environ-
ment, via the action of a limited number of secreted or plasma membrane proteases
with the unique ability to cleave native collagen, and intracellularly, via an assort-
ment of lysosomal cathepsins that degrade collagen made available through its
uptake by specific collagen endocytic receptors. Emerging evidence indicates that
these two principal mechanisms for collagen degradation cooperate to form a single
pathway that executes the sequential and complete degradation of collagen during
both physiological tissue remodeling and pathological remodeling, including tumor
progression. The chapter summarizes the prevailing paradigms regarding the turn-
over of this abundant extracellular matrix molecule.
3.1
Introduction
The collagens constitute as much as 90% of the extracellular matrix of a tissue and
are by far the most abundant components of the interstitial extracellular matrix and
basement membrane of the vertebrate body. They represent a structurally unique
group of proteins that are composed of three polypeptide chains, each with a single
long uninterrupted section of Gly-X-Y amino acid repeats, which intertwine to
produce a superhelix that buries the peptide bonds within the interior of the helix.
The fibrillar collagens spontaneously self-associate to form fibrils that range in diame-
ter from 10 to 300 nm, while basement membrane collagens form complicated sheets
T.H. Bugge ( * )
Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute
of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
e-mail: thomas.bugge@nih.gov
N. Behrendt
The Finsen Laboratory, Rigshospitalet Section 3735, Copenhagen Biocenter, Ole Maaloes Vej 5,
2200 Copenhagen N, Denmark
e-mail: niels.behrendt@finsenlab.dk
Search WWH ::




Custom Search