Presenilin-dependent intramembrane cleavage of ephrin-B1
<p>Abstract</p> <p>Background</p> <p>Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that are involved in cellula...
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Series: | Molecular Neurodegeneration |
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doaj-74b9ec4e62d74faca7ea81b0a609edf52020-11-24T21:57:29ZengBMCMolecular Neurodegeneration1750-13262006-06-0111210.1186/1750-1326-1-2Presenilin-dependent intramembrane cleavage of ephrin-B1Tomita TaisukeTanaka SayakaMorohashi YuichiIwatsubo Takeshi<p>Abstract</p> <p>Background</p> <p>Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that are involved in cellular signaling. Considering γ-secretase inhibitors as therapeutics for Alzheimer's disease, understanding the physiologically and biologically important substrate for γ-secretase activity in brains is emerging issue. To elucidate the molecular mechanism and physiological role of γ-secretase, we screened candidate molecules for γ-secretase substrates.</p> <p>Results</p> <p>We show that ephrin-B1, that participates in cell-cell repulsive and attractive signaling together with its Eph receptor, constitutively undergoes ectodomain shedding and that the residual membrane-tethered fragment is sequentially cleaved by γ-secretase to release the intracellular domain. Furthermore, overexpression of membrane-tethered ephrin-B1 caused protrusion of numerous cellular processes consisted of F-actin, that required the preservation of the most C-terminal region of ephrin-B1. In contrast, soluble intracellular domain translocated into the nucleus and had no effect on cell morphology.</p> <p>Conclusion</p> <p>Our findings suggest that ephrin-B is a genuine substrate for γ-secretase and regulates the cytoskeletal dynamics through intramembrane proteolysis.</p> http://www.molecularneurodegeneration.com/content/1/1/2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tomita Taisuke Tanaka Sayaka Morohashi Yuichi Iwatsubo Takeshi |
spellingShingle |
Tomita Taisuke Tanaka Sayaka Morohashi Yuichi Iwatsubo Takeshi Presenilin-dependent intramembrane cleavage of ephrin-B1 Molecular Neurodegeneration |
author_facet |
Tomita Taisuke Tanaka Sayaka Morohashi Yuichi Iwatsubo Takeshi |
author_sort |
Tomita Taisuke |
title |
Presenilin-dependent intramembrane cleavage of ephrin-B1 |
title_short |
Presenilin-dependent intramembrane cleavage of ephrin-B1 |
title_full |
Presenilin-dependent intramembrane cleavage of ephrin-B1 |
title_fullStr |
Presenilin-dependent intramembrane cleavage of ephrin-B1 |
title_full_unstemmed |
Presenilin-dependent intramembrane cleavage of ephrin-B1 |
title_sort |
presenilin-dependent intramembrane cleavage of ephrin-b1 |
publisher |
BMC |
series |
Molecular Neurodegeneration |
issn |
1750-1326 |
publishDate |
2006-06-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that are involved in cellular signaling. Considering γ-secretase inhibitors as therapeutics for Alzheimer's disease, understanding the physiologically and biologically important substrate for γ-secretase activity in brains is emerging issue. To elucidate the molecular mechanism and physiological role of γ-secretase, we screened candidate molecules for γ-secretase substrates.</p> <p>Results</p> <p>We show that ephrin-B1, that participates in cell-cell repulsive and attractive signaling together with its Eph receptor, constitutively undergoes ectodomain shedding and that the residual membrane-tethered fragment is sequentially cleaved by γ-secretase to release the intracellular domain. Furthermore, overexpression of membrane-tethered ephrin-B1 caused protrusion of numerous cellular processes consisted of F-actin, that required the preservation of the most C-terminal region of ephrin-B1. In contrast, soluble intracellular domain translocated into the nucleus and had no effect on cell morphology.</p> <p>Conclusion</p> <p>Our findings suggest that ephrin-B is a genuine substrate for γ-secretase and regulates the cytoskeletal dynamics through intramembrane proteolysis.</p> |
url |
http://www.molecularneurodegeneration.com/content/1/1/2 |
work_keys_str_mv |
AT tomitataisuke presenilindependentintramembranecleavageofephrinb1 AT tanakasayaka presenilindependentintramembranecleavageofephrinb1 AT morohashiyuichi presenilindependentintramembranecleavageofephrinb1 AT iwatsubotakeshi presenilindependentintramembranecleavageofephrinb1 |
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1725855345508614144 |