A novel substrate for analyzing Alzheimer's disease γ-secretase

Stefan F. Lichtenthaler; Gerd Multhaup; Colin L. Masters; Konrad Beyreuther

doi:10.1016/S0014-5793(99)00730-9

A novel substrate for analyzing Alzheimer's disease γ-secretase

Stefan F. Lichtenthaler, Gerd Multhaup, Colin L. Masters, Konrad Beyreuther

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

42 Scopus citations

Abstract

Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by β-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called γ-secretase. To study the enzymatic properties of γ-secretase independently of β-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by γ-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals showing amyloid pathology.

Original language	English
Pages (from-to)	288-292
Number of pages	5
Journal	FEBS Letters
Volume	453
Issue number	3
DOIs	https://doi.org/10.1016/S0014-5793(99)00730-9
State	Published - 25 Jun 1999
Externally published	Yes

Keywords

Alzheimer's disease
Amyloid precursor protein
Protein transport
Signal peptidase
γ-secretase

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10.1016/S0014-5793(99)00730-9

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@article{f507c50ef9f94661a04a3faaac1693cb,

title = "A novel substrate for analyzing Alzheimer's disease γ-secretase",

abstract = "Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by β-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called γ-secretase. To study the enzymatic properties of γ-secretase independently of β-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by γ-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals showing amyloid pathology.",

keywords = "Alzheimer's disease, Amyloid precursor protein, Protein transport, Signal peptidase, γ-secretase",

author = "Lichtenthaler, {Stefan F.} and Gerd Multhaup and Masters, {Colin L.} and Konrad Beyreuther",

note = "Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (through SFB 317) and the Fonds der Chemischen Industrie of Germany.",

year = "1999",

month = jun,

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doi = "10.1016/S0014-5793(99)00730-9",

language = "English",

volume = "453",

pages = "288--292",

journal = "FEBS Letters",

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T1 - A novel substrate for analyzing Alzheimer's disease γ-secretase

AU - Lichtenthaler, Stefan F.

AU - Multhaup, Gerd

AU - Masters, Colin L.

AU - Beyreuther, Konrad

N1 - Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (through SFB 317) and the Fonds der Chemischen Industrie of Germany.

PY - 1999/6/25

Y1 - 1999/6/25

N2 - Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by β-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called γ-secretase. To study the enzymatic properties of γ-secretase independently of β-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by γ-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals showing amyloid pathology.

AB - Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by β-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called γ-secretase. To study the enzymatic properties of γ-secretase independently of β-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by γ-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals showing amyloid pathology.

KW - Alzheimer's disease

KW - Amyloid precursor protein

KW - Protein transport

KW - Signal peptidase

KW - γ-secretase

UR - http://www.scopus.com/inward/record.url?scp=0032792982&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(99)00730-9

DO - 10.1016/S0014-5793(99)00730-9

M3 - Article

C2 - 10405162

AN - SCOPUS:0032792982

SN - 0014-5793

VL - 453

SP - 288

EP - 292

JO - FEBS Letters

JF - FEBS Letters

IS - 3

ER -

A novel substrate for analyzing Alzheimer's disease γ-secretase

Abstract

Keywords

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