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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2004-12-8
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pubmed:abstractText |
gamma-Secretase is an intramembrane cleaving protease involved in Alzheimer's disease. gamma-Secretase occurs as a high molecular weight complex composed of presenilin (PS1/2), nicastrin (NCT), anterior pharynx-defective phenotype 1 and PS enhancer 2. Little is known about the cellular mechanisms of gamma-secretase assembly. Here we demonstrate that the cytoplasmic tail of PS1 fulfills several functions required for complex formation, retention of unincorporated PS1 and gamma-secretase activity. The very C-terminus interacts with the transmembrane domain of NCT and may penetrate into the membrane. Deletion of the last amino acid is sufficient to completely block gamma-secretase assembly and release of PS1 from the endoplasmic reticulum (ER). This suggests that unincorporated PS1 is actively retained within the ER. We identified a hydrophobic stretch of amino acids within the cytoplasmic tail of PS1 distinct from the NCT-binding site, which is required to retain unincorporated PS1 within the ER. Deletion of the retention signal results in the release of PS1 from the ER and the assembly of a nonfunctional gamma-secretase complex, suggesting that at least a part of the retention motif may also be required for the function of PS1.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-10197533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-10438548,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-10594046,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-11432849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-11719200,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-11943765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12048259,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12147673,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12198112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12219096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12388554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12584255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12612637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12679784,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12691659,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-12917438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-14602727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-1465129,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-14699055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-14749724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-15056474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-15189355,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-15248287,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-15322123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-1878135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-1915263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-2225064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-2527615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-8253791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-8938133,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-9224763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-9575200,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-9618547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-9620803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15549135-9841901
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4738-48
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15549135-Amino Acid Sequence,
pubmed-meshheading:15549135-Amyloid Precursor Protein Secretases,
pubmed-meshheading:15549135-Animals,
pubmed-meshheading:15549135-COS Cells,
pubmed-meshheading:15549135-Cercopithecus aethiops,
pubmed-meshheading:15549135-Endopeptidases,
pubmed-meshheading:15549135-Endoplasmic Reticulum,
pubmed-meshheading:15549135-Membrane Glycoproteins,
pubmed-meshheading:15549135-Membrane Proteins,
pubmed-meshheading:15549135-Molecular Sequence Data,
pubmed-meshheading:15549135-Presenilin-1,
pubmed-meshheading:15549135-Protein Binding,
pubmed-meshheading:15549135-Protein Sorting Signals,
pubmed-meshheading:15549135-Protein Structure, Tertiary,
pubmed-meshheading:15549135-Recombinant Fusion Proteins,
pubmed-meshheading:15549135-Sequence Alignment
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pubmed:year |
2004
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pubmed:articleTitle |
The presenilin C-terminus is required for ER-retention, nicastrin-binding and gamma-secretase activity.
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pubmed:affiliation |
Laboratory for Alzheimer's and Parkinson's Disease Research, Department of Biochemistry, Adolf-Butenandt-Institute, Ludwig-Maximilians-Universität, München, Germany. ckaether@med.uni-muenchen.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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