Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts

Carles Gil; Roger Cubí; José Aguilera

doi:10.1016/j.febslet.2007.03.080

Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts

Carles Gil, Roger Cubí, José Aguilera

Research output: Contribution to journal › Article › Research › peer-review

21 Citations (Scopus)

Abstract

Protein ectodomain shedding is the proteolytic release of the extracellular domain of membrane-bound proteins. Neurotrophin receptor p75^NTR is known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that p75^NTR is present in detergent-resistant membranes (DRM), also known as lipid rafts, only in its full-length form. Disrupting the integrity of lipid rafts causes solubilization of p75^NTR after detergent treatment and enhancement of the shedding. Analyses of the enzymes described as being responsible for p75^NTR shedding, i.e. tumor necrosis factor α convertase (TACE) and presenilin-1 (PS1), revealed that TACE is absent in DRM, while variable proportions of the C-terminal and N-terminal fragments of PS1 are found. In summary, our results point to a role of lipid rafts in the modulation of the shedding of the p75^NTR receptor.

Original language	English
Pages (from-to)	1851-1858
Number of pages	8
Journal	FEBS Letters
Volume	581
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2007.03.080 https://doi.org/10.1016/j.febslet.2007.03.080
Publication status	Published - 1 May 2007

Keywords

Lipid rafts
NRH2
Neurotrophins
Receptor shedding
TACE
γ-Secretase

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title = "Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts",

abstract = "Protein ectodomain shedding is the proteolytic release of the extracellular domain of membrane-bound proteins. Neurotrophin receptor p75NTR is known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that p75NTR is present in detergent-resistant membranes (DRM), also known as lipid rafts, only in its full-length form. Disrupting the integrity of lipid rafts causes solubilization of p75NTR after detergent treatment and enhancement of the shedding. Analyses of the enzymes described as being responsible for p75NTR shedding, i.e. tumor necrosis factor α convertase (TACE) and presenilin-1 (PS1), revealed that TACE is absent in DRM, while variable proportions of the C-terminal and N-terminal fragments of PS1 are found. In summary, our results point to a role of lipid rafts in the modulation of the shedding of the p75NTR receptor.",

keywords = "Lipid rafts, NRH2, Neurotrophins, Receptor shedding, TACE, γ-Secretase",

author = "Carles Gil and Roger Cub{\'i} and Jos{\'e} Aguilera",

note = "Funding Information: This work was supported by Grant SAF2006-15184 from the Ministerio de Ciencia y Tecnologı´a (Direcci{\'o}n General de Investigaci{\'o}n) from the Spanish Government (MCYT). We thank G. Schiavo (Cancer Research UK; London, UK) for the generous gift of the Thy-1 antibody, and for the assistance and comments on the lipid rafts extraction. We thank J. Sabri{\`a} (UAB; Barcelona, Spain) for her help in the isolation of the synaptosomal-enriched fraction. We also thank C. Simmons for his help in the English preparation of this manuscript. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2007",

month = may,

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doi = "10.1016/j.febslet.2007.03.080",

language = "English",

volume = "581",

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T1 - Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts

AU - Gil, Carles

AU - Cubí, Roger

AU - Aguilera, José

N1 - Funding Information: This work was supported by Grant SAF2006-15184 from the Ministerio de Ciencia y Tecnologı´a (Dirección General de Investigación) from the Spanish Government (MCYT). We thank G. Schiavo (Cancer Research UK; London, UK) for the generous gift of the Thy-1 antibody, and for the assistance and comments on the lipid rafts extraction. We thank J. Sabrià (UAB; Barcelona, Spain) for her help in the isolation of the synaptosomal-enriched fraction. We also thank C. Simmons for his help in the English preparation of this manuscript. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Protein ectodomain shedding is the proteolytic release of the extracellular domain of membrane-bound proteins. Neurotrophin receptor p75NTR is known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that p75NTR is present in detergent-resistant membranes (DRM), also known as lipid rafts, only in its full-length form. Disrupting the integrity of lipid rafts causes solubilization of p75NTR after detergent treatment and enhancement of the shedding. Analyses of the enzymes described as being responsible for p75NTR shedding, i.e. tumor necrosis factor α convertase (TACE) and presenilin-1 (PS1), revealed that TACE is absent in DRM, while variable proportions of the C-terminal and N-terminal fragments of PS1 are found. In summary, our results point to a role of lipid rafts in the modulation of the shedding of the p75NTR receptor.

AB - Protein ectodomain shedding is the proteolytic release of the extracellular domain of membrane-bound proteins. Neurotrophin receptor p75NTR is known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that p75NTR is present in detergent-resistant membranes (DRM), also known as lipid rafts, only in its full-length form. Disrupting the integrity of lipid rafts causes solubilization of p75NTR after detergent treatment and enhancement of the shedding. Analyses of the enzymes described as being responsible for p75NTR shedding, i.e. tumor necrosis factor α convertase (TACE) and presenilin-1 (PS1), revealed that TACE is absent in DRM, while variable proportions of the C-terminal and N-terminal fragments of PS1 are found. In summary, our results point to a role of lipid rafts in the modulation of the shedding of the p75NTR receptor.

KW - Lipid rafts

KW - NRH2

KW - Neurotrophins

KW - Receptor shedding

KW - TACE

KW - γ-Secretase

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DO - 10.1016/j.febslet.2007.03.080

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C2 - 17433308

SN - 0014-5793

VL - 581

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EP - 1858

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts

Abstract

Keywords

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