Shedding of collagen XXIII is mediated by furin and depends on the plasma membrane microenvironment.
Collagen XXIII belongs to the class of type II orientated transmembrane collagens. A common feature of these proteins is the presence of two forms of the molecule: a membrane-bound form and a shed form. Here we demonstrate that, in mouse lung, collagen XXIII is found predominantly as the full-length form, whereas in brain, it is present mostly as the shed form, suggesting that shedding is tissue-specific and tissue-regulated. To analyze the shedding process of collagen XXIII, a cell culture model was established. Mutations introduced into two putative proprotein convertase cleavage sites showed that altering the second cleavage site inactivated much of the shedding. This supports the idea that furin, a major physiological protease, is predominantly responsible for shedding. Furthermore, our studies indicate that collagen XXIII is localized in lipid rafts in the plasma membrane and that ectodomain shedding is altered by a cholesterol-dependent mechanism. Moreover, newly synthesized collagen XXIII either is cleaved inside the Golgi/trans-Golgi network or reaches the cell surface, where it becomes protected from processing by being localized in lipid rafts. These mechanisms allow the cell to regulate the amounts of cell surface-bound and secreted collagen XXIII.
Veit
Guido
G
Center for Biochemistry, the University of Cologne, 50931 Cologne, Germany, the.
Zimina
Elena P
EP
Department of Dermatology, University of Freiburg, 79104 Freiburg, Germany, the.
Franzke
Claus-Werner
CW
Department of Dermatology, University of Freiburg, 79104 Freiburg, Germany, the.
Kutsch
Stefanie
S
Center for Biochemistry, the University of Cologne, 50931 Cologne, Germany, the.
Siebolds
Udo
U
Institute of Pathology, University of Cologne, 50924 Cologne, Germany, and the.
Gordon
Marion K
MK
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, and the Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey 08854.
Bruckner-Tuderman
Leena
L
Department of Dermatology, University of Freiburg, 79104 Freiburg, Germany, the.
Koch
Manuel
M
Center for Biochemistry, the University of Cologne, 50931 Cologne, Germany, the; Department of Dermatology, and the University of Cologne, 50931 Cologne, Germany, the; Center for Molecular Medicine, Medical Faculty, University of Cologne, 50931 Cologne, Germany, the. Electronic address: Manuel.Koch@uni-koeln.de.
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000378:metabolism*; D045683:Furin / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D021962:Membrane Microdomains / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D043484:Proprotein Convertases / Q000502:physiology
D003094:Collagen; D043484:Proprotein Convertases; D045683:Furin