Summary
The ADAMs (A Disintegrin And Metalloprotease-like) family is a large and rapidly expanding group of metallo-proteinases with structural similarity. The are normally characterized by the presence of a proteolytic domain and disintegrin and signalling domains. Although 21 ADAMs proteins have been already cloned to date, in most cases their natural substrates are unknown. The best characterized representative of the mammalian ADAMs family is the TNF-α converting enzyme (TACE). TACE is an integral membrane metalloproteinase that causes the secretion of the active form of TNF-α from its plasma membrane precursor and thus can be regarded as a membrane protein secretase. Secretion of membrane proteins is a very well documented biological phenomenon and was demonstrated for a diverse range of membrane proteins, two examples being angiotensin converting enzyme (ACE) and Alzheimer's amyloid precursor protein (APP). ACE and APP secretion was shown to possess substantial similarity with the secretion of TNF-α. In the present study, we have attempted to demonstrate that a metalloproteinase might be involved in the shedding of another membrane-bound protein—acetylcholinesterase (AChE). Secretion of AChE by human neuroblastoma SH-SY5Y cells was found to be inhibited by a selective hydroxamate metalloproteinase inhibitor batimastat (20 μM), and stimulated by carbachol (20 μM), which have previously been shown to regulate the activity of APP α-secretase in a similar manner. The role of ADAMs proteins in the shedding of molecules from the cell surface is discussed.
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Abbreviations
- Aβ:
-
amyloid β protein
- ACE:
-
angiotensin converting enzyme
- AChE:
-
acetylcholinesterase
- ADAM:
-
A Disintegrin And Metalloproteinase
- APP:
-
amyloid precursor protein
- ATCh:
-
acetylthiocholine
- MDC:
-
Metalloproteinase-like, Disintegrin-like, Cysteine-rich protein
- PAR:
-
proteinase-activated receptor
- PKC:
-
protein kinase C
- TACE:
-
TNF-α converting enzyme
- TGF:
-
transforming growth factor
- TNF:
-
tumour necrosis factor
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Nalivaeva, N.N., Turner, A.J. Does acetylcholinesterase secretion involve an ADAMs-like metallosecretase?. Lett Pept Sci 6, 343–348 (1999). https://doi.org/10.1007/BF02443430
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DOI: https://doi.org/10.1007/BF02443430