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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Main Authors: Tomita Taisuke, Tanaka Sayaka, Morohashi Yuichi, Iwatsubo Takeshi
Format: Article
Language:English
Published: BMC 2006-06-01
Series:Molecular Neurodegeneration
Online Access:http://www.molecularneurodegeneration.com/content/1/1/2
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spelling 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
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AT tanakasayaka presenilindependentintramembranecleavageofephrinb1
AT morohashiyuichi presenilindependentintramembranecleavageofephrinb1
AT iwatsubotakeshi presenilindependentintramembranecleavageofephrinb1
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