In vivo regulation of the A disintegrin and metalloproteinase 10 (ADAM10) by the tetraspanin 15
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00494335" target="_blank" >RIV/68378050:_____/18:00494335 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1007/s00018-018-2791-2" target="_blank" >http://dx.doi.org/10.1007/s00018-018-2791-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-018-2791-2" target="_blank" >10.1007/s00018-018-2791-2</a>
Alternative languages
Result language
angličtina
Original language name
In vivo regulation of the A disintegrin and metalloproteinase 10 (ADAM10) by the tetraspanin 15
Original language description
A disintegrin and metalloproteinase 10 (ADAM10) plays a major role in the ectodomain shedding of important surface molecules with physiological and pathological relevance including the amyloid precursor protein (APP), the cellular prion protein, and different cadherins. Despite its therapeutic potential, there is still a considerable lack of knowledge how this protease is regulated. We have previously identified tetraspanin15 (Tspan15) as a member of the TspanC8 family to specifically associate with ADAM10. Cell-based overexpression experiments revealed that this binding affected the maturation process and surface expression of the protease. Our current study shows that Tspan15 is abundantly expressed in mouse brain, where it specifically interacts with endogenous ADAM10. Tspan15 knockout mice did not reveal an overt phenotype but showed a pronounced decrease of the active and mature form of ADAM10, an effect which augmented with aging. The decreased expression of active ADAM10 correlated with an age-dependent reduced shedding of neuronal (N)-cadherin and the cellular prion protein. APP alpha-secretase cleavage and the expression of Notch-dependent genes were not affected by the loss of Tspan15, which is consistent with the hypothesis that different TspanC8s cause ADAM10 to preferentially cleave particular substrates. Analyzing spine morphology revealed no obvious differences between Tspan15 knockout and wild-type mice. However, Tspan15 expression was elevated in brains of an Alzheimer's disease mouse model and of patients, suggesting that upregulation of Tspan15 expression reflects a cellular response in a disease state. In conclusion, our data show that Tspan15 and most likely also other members of the TspanC8 family are central modulators of ADAM10-mediated ectodomain shedding in vivo.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/ED2.1.00%2F19.0395" target="_blank" >ED2.1.00/19.0395: Higher quality and capacity for transgenic models</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and Molecular Life Sciences
ISSN
1420-682X
e-ISSN
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Volume of the periodical
75
Issue of the periodical within the volume
17
Country of publishing house
CH - SWITZERLAND
Number of pages
17
Pages from-to
3251-3267
UT code for WoS article
000440101300010
EID of the result in the Scopus database
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