Overexpression of calsenilin enhances γ-secretase activity
Presenilin/γ-secretase is a membrane-associated protease that cleaves within the transmembrane region of the amyloid precursor protein (APP) to generate amyloid-β peptide (Aβ) whose deposition in the brain is a characteristic of Alzheimer's disease (AD). Calsenilin, a calcium binding protein th...
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| Veröffentlicht in: | Neuroscience letters 2005-04, Vol.378 (1), p.59-64 |
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| container_title | Neuroscience letters |
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| creator | Jo, Dong-Gyu Jang, Jiyeon Kim, Byung-Ju Lundkvist, Johan Jung, Yong-Keun |
| description | Presenilin/γ-secretase is a membrane-associated protease that cleaves within the transmembrane region of the amyloid precursor protein (APP) to generate amyloid-β peptide (Aβ) whose deposition in the brain is a characteristic of Alzheimer's disease (AD). Calsenilin, a calcium binding protein that has been shown to interact with the C-termini of both presenilin 1 (PS1) and presenilin 2 (PS2), appears to play a role in transcriptional regulation and apoptosis and to bind to A-type voltage-gated potassium channels. Here, we report that overexpression of calsenilin enhanced γ-secretase activity in cells. The effect of calsenilin on the γ-cleavage of substrates was blocked by the selective γ-secretase inhibitor L-685,458. We also employed a cellular γ-cleavage GFP-reporter assay to demonstrate the effect of calsenilin on γ-secretase activity. To establish a direct role for calsenilin in regulating γ-secretase activity, we incubated purified calsenilin with isolated membrane fractions and found increased Aβ production in a cell free system. These data suggest that calsenilin may be one of the regulatory factors for γ-secretase. |
| doi_str_mv | 10.1016/j.neulet.2004.12.078 |
| format | Article |
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Calsenilin, a calcium binding protein that has been shown to interact with the C-termini of both presenilin 1 (PS1) and presenilin 2 (PS2), appears to play a role in transcriptional regulation and apoptosis and to bind to A-type voltage-gated potassium channels. Here, we report that overexpression of calsenilin enhanced γ-secretase activity in cells. The effect of calsenilin on the γ-cleavage of substrates was blocked by the selective γ-secretase inhibitor L-685,458. We also employed a cellular γ-cleavage GFP-reporter assay to demonstrate the effect of calsenilin on γ-secretase activity. To establish a direct role for calsenilin in regulating γ-secretase activity, we incubated purified calsenilin with isolated membrane fractions and found increased Aβ production in a cell free system. These data suggest that calsenilin may be one of the regulatory factors for γ-secretase.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/j.neulet.2004.12.078</identifier><identifier>PMID: 15763173</identifier><identifier>CODEN: NELED5</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Alzheimer's disease ; Amyloid beta-Peptides - biosynthesis ; Amyloid Precursor Protein Secretases ; Animals ; Aspartic Acid Endopeptidases ; Biological and medical sciences ; Calcium ; Calcium-Binding Proteins - biosynthesis ; Calsenilin ; Cell-Free System ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Endopeptidases - drug effects ; Endopeptidases - metabolism ; Enzyme Inhibitors - pharmacology ; Fundamental and applied biological sciences. Psychology ; Gamma-secretase ; Genes, Reporter ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; Kv Channel-Interacting Proteins ; Medical sciences ; Neurology ; Presenilin ; Repressor Proteins - biosynthesis ; Transfection ; Vertebrates: nervous system and sense organs</subject><ispartof>Neuroscience letters, 2005-04, Vol.378 (1), p.59-64</ispartof><rights>2005 Elsevier Ireland Ltd</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-2b4b191359f1620ef257e6c81f8e8844dcf2988ff4c8e0e80be4c5ecf0f28a743</citedby><cites>FETCH-LOGICAL-c459t-2b4b191359f1620ef257e6c81f8e8844dcf2988ff4c8e0e80be4c5ecf0f28a743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neulet.2004.12.078$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16598073$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15763173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1950225$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Jo, Dong-Gyu</creatorcontrib><creatorcontrib>Jang, Jiyeon</creatorcontrib><creatorcontrib>Kim, Byung-Ju</creatorcontrib><creatorcontrib>Lundkvist, Johan</creatorcontrib><creatorcontrib>Jung, Yong-Keun</creatorcontrib><title>Overexpression of calsenilin enhances γ-secretase activity</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>Presenilin/γ-secretase is a membrane-associated protease that cleaves within the transmembrane region of the amyloid precursor protein (APP) to generate amyloid-β peptide (Aβ) whose deposition in the brain is a characteristic of Alzheimer's disease (AD). Calsenilin, a calcium binding protein that has been shown to interact with the C-termini of both presenilin 1 (PS1) and presenilin 2 (PS2), appears to play a role in transcriptional regulation and apoptosis and to bind to A-type voltage-gated potassium channels. Here, we report that overexpression of calsenilin enhanced γ-secretase activity in cells. The effect of calsenilin on the γ-cleavage of substrates was blocked by the selective γ-secretase inhibitor L-685,458. We also employed a cellular γ-cleavage GFP-reporter assay to demonstrate the effect of calsenilin on γ-secretase activity. To establish a direct role for calsenilin in regulating γ-secretase activity, we incubated purified calsenilin with isolated membrane fractions and found increased Aβ production in a cell free system. These data suggest that calsenilin may be one of the regulatory factors for γ-secretase.</description><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - biosynthesis</subject><subject>Amyloid Precursor Protein Secretases</subject><subject>Animals</subject><subject>Aspartic Acid Endopeptidases</subject><subject>Biological and medical sciences</subject><subject>Calcium</subject><subject>Calcium-Binding Proteins - biosynthesis</subject><subject>Calsenilin</subject><subject>Cell-Free System</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Endopeptidases - drug effects</subject><subject>Endopeptidases - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gamma-secretase</subject><subject>Genes, Reporter</subject><subject>Green Fluorescent Proteins</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kv Channel-Interacting Proteins</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Presenilin</subject><subject>Repressor Proteins - biosynthesis</subject><subject>Transfection</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0d-K1DAUBvAgLu646xuI9EbvWs9JkyZFEGTxHyzsze51SDMnmLHTjkk7us_le_hMZmxx7_QqIfzOIXwfY88RKgRsXu-qgeaepooDiAp5BUo_YhvUipeqVfwx20ANoqxbAefsaUo7AJAoxRN2jlI1Nap6w97cHCnSj0OklMI4FKMvnO0TDaEPQ0HDFzs4SsWvn2UiF2myiQrrpnAM0_0lO_Mn-2w9L9jdh_e3V5_K65uPn6_eXZdOyHYqeSc6bLGWrceGA3kuFTVOo9ektRBb53mrtffCaQLS0JFwkpwHz7VVor5g5bI3fafD3JlDDHsb781og1mfvuYbGamx0Sf_avGHOH6bKU1mH5KjvrcDjXMyjZIICvG_EJXGHJjOUCzQxTGlSP7vHxDMqQ2zM0sb5tSGQW5yG3nsxbp_7va0fRha48_g5QpsyrH7mNMO6cE1stXwx71dHOWYj4GiSS5QbmYbIrnJbMfw75_8Butiq34</recordid><startdate>20050411</startdate><enddate>20050411</enddate><creator>Jo, Dong-Gyu</creator><creator>Jang, Jiyeon</creator><creator>Kim, Byung-Ju</creator><creator>Lundkvist, Johan</creator><creator>Jung, Yong-Keun</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20050411</creationdate><title>Overexpression of calsenilin enhances γ-secretase activity</title><author>Jo, Dong-Gyu ; Jang, Jiyeon ; Kim, Byung-Ju ; Lundkvist, Johan ; Jung, Yong-Keun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-2b4b191359f1620ef257e6c81f8e8844dcf2988ff4c8e0e80be4c5ecf0f28a743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - biosynthesis</topic><topic>Amyloid Precursor Protein Secretases</topic><topic>Animals</topic><topic>Aspartic Acid Endopeptidases</topic><topic>Biological and medical sciences</topic><topic>Calcium</topic><topic>Calcium-Binding Proteins - biosynthesis</topic><topic>Calsenilin</topic><topic>Cell-Free System</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Endopeptidases - drug effects</topic><topic>Endopeptidases - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gamma-secretase</topic><topic>Genes, Reporter</topic><topic>Green Fluorescent Proteins</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kv Channel-Interacting Proteins</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Presenilin</topic><topic>Repressor Proteins - biosynthesis</topic><topic>Transfection</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jo, Dong-Gyu</creatorcontrib><creatorcontrib>Jang, Jiyeon</creatorcontrib><creatorcontrib>Kim, Byung-Ju</creatorcontrib><creatorcontrib>Lundkvist, Johan</creatorcontrib><creatorcontrib>Jung, Yong-Keun</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jo, Dong-Gyu</au><au>Jang, Jiyeon</au><au>Kim, Byung-Ju</au><au>Lundkvist, Johan</au><au>Jung, Yong-Keun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of calsenilin enhances γ-secretase activity</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2005-04-11</date><risdate>2005</risdate><volume>378</volume><issue>1</issue><spage>59</spage><epage>64</epage><pages>59-64</pages><issn>0304-3940</issn><eissn>1872-7972</eissn><coden>NELED5</coden><abstract>Presenilin/γ-secretase is a membrane-associated protease that cleaves within the transmembrane region of the amyloid precursor protein (APP) to generate amyloid-β peptide (Aβ) whose deposition in the brain is a characteristic of Alzheimer's disease (AD). Calsenilin, a calcium binding protein that has been shown to interact with the C-termini of both presenilin 1 (PS1) and presenilin 2 (PS2), appears to play a role in transcriptional regulation and apoptosis and to bind to A-type voltage-gated potassium channels. Here, we report that overexpression of calsenilin enhanced γ-secretase activity in cells. The effect of calsenilin on the γ-cleavage of substrates was blocked by the selective γ-secretase inhibitor L-685,458. We also employed a cellular γ-cleavage GFP-reporter assay to demonstrate the effect of calsenilin on γ-secretase activity. To establish a direct role for calsenilin in regulating γ-secretase activity, we incubated purified calsenilin with isolated membrane fractions and found increased Aβ production in a cell free system. These data suggest that calsenilin may be one of the regulatory factors for γ-secretase.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>15763173</pmid><doi>10.1016/j.neulet.2004.12.078</doi><tpages>6</tpages></addata></record> |
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| ispartof | Neuroscience letters, 2005-04, Vol.378 (1), p.59-64 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Alzheimer's disease Amyloid beta-Peptides - biosynthesis Amyloid Precursor Protein Secretases Animals Aspartic Acid Endopeptidases Biological and medical sciences Calcium Calcium-Binding Proteins - biosynthesis Calsenilin Cell-Free System Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Endopeptidases - drug effects Endopeptidases - metabolism Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Gamma-secretase Genes, Reporter Green Fluorescent Proteins HeLa Cells Humans Kv Channel-Interacting Proteins Medical sciences Neurology Presenilin Repressor Proteins - biosynthesis Transfection Vertebrates: nervous system and sense organs |
| title | Overexpression of calsenilin enhances γ-secretase activity |
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