Several transmembrane molecules are cleaved at juxtamembrane extracellular sites leading to shedding of ectodomains. We analysed shedding of members of the Vps10p-D (Vps10p domain; where Vps is vacuolar protein sorting) family of neuronal type-I receptors with partially overlapping functions, and additional proteolytic events initiated by the shedding. When transfected into CHO (Chinese-hamster ovary) cells (CHO-K1), sorCS1a–sorCS1c isoforms were shed at high rates (∼0.61%·min−1) that were increased approx. 3-fold upon stimulation with phorbol ester. sorCS1c identified in the cultured neuroblastoma cell line SH-SY5Y was shed similarly. In CHO-K1 transfectants, constitutive and stimulated shedding of sorCS3 also occurred at high rates (0.29% and 1.03%·min−1). By comparison, constitutive and stimulated shedding of sorLA occurred at somewhat lower rates (0.07% and 0.48%·min−1), whereas sorCS2 and sortilin were shed at very low rates even when stimulated (∼0.01%·min−1). Except for sorCS2, shedding of the receptors was dramatically reduced in mutant CHO cells (CHO-M2) devoid of active TACE (tumour necrosis factor α-converting enzyme), demonstrating that this enzyme accounts for most sheddase activity. The release of sorCS1 and sorLA ectodomains initiated rapid cleavage of the membrane-tethered C-terminal stubs that accumulated only in the presence of γ-secretase inhibitors. Purified shed sorLA bound several ligands similarly to the entire luminal domain of the receptor, including PDGF-BB (platelet-derived growth factor-BB) and amyloid-β precursor protein. In addition, PDGF-BB also bound to the luminal domains of sorCS1 and sorCS3. The results suggest that ectodomains shed from a subset of Vps10p-D receptors can function as carrier proteins.
Article navigation
Research Article|
March 28 2006
Tumour necrosis factor α-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family members
Guido Hermey
;
Guido Hermey
1
1
Institute of Medical Biochemistry, MIND Center, Ole Worms Allé, Building 1170, University of Aarhus, 8000 Århus C, Denmark
Search for other works by this author on:
Susanne S. Sjøgaard
;
Susanne S. Sjøgaard
1
Institute of Medical Biochemistry, MIND Center, Ole Worms Allé, Building 1170, University of Aarhus, 8000 Århus C, Denmark
Search for other works by this author on:
Claus Munck Petersen
;
Claus Munck Petersen
1
Institute of Medical Biochemistry, MIND Center, Ole Worms Allé, Building 1170, University of Aarhus, 8000 Århus C, Denmark
Search for other works by this author on:
Anders Nykjær
;
Anders Nykjær
1
Institute of Medical Biochemistry, MIND Center, Ole Worms Allé, Building 1170, University of Aarhus, 8000 Århus C, Denmark
Search for other works by this author on:
Jørgen Gliemann
Jørgen Gliemann
2
1
Institute of Medical Biochemistry, MIND Center, Ole Worms Allé, Building 1170, University of Aarhus, 8000 Århus C, Denmark2
To whom correspondence should be addressed (email jgliemann@biokemi.au.dk).
Search for other works by this author on:
Biochem J (2006) 395 (2): 285-293.
Article history
Received:
August 19 2005
Revision Received:
December 05 2005
Accepted:
January 04 2006
Accepted Manuscript online:
January 04 2006
Citation
Guido Hermey, Susanne S. Sjøgaard, Claus Munck Petersen, Anders Nykjær, Jørgen Gliemann; Tumour necrosis factor α-converting enzyme mediates ectodomain shedding of Vps10p-domain receptor family members. Biochem J 15 April 2006; 395 (2): 285–293. doi: https://doi.org/10.1042/BJ20051364
Download citation file:
Close
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionCited By
Related Articles
Deglycosylation, processing and crystallization of human testis angiotensin-converting enzyme
Biochem J (April, 2003)
Characterization of the catalytic activity of the membrane-anchored metalloproteinase ADAM15 in cell-based assays
Biochem J (April, 2009)
Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays
Biochem J (April, 2017)
Human sorCS1 binds sortilin and hampers its cellular functions
Biochem J (December, 2013)