Calstabin 2: An important regulator for learning and memory in mice
Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (P...
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| Veröffentlicht in: | Scientific reports 2016-02, Vol.6 (1), p.21087-21087, Article 21087 |
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| creator | Yuan, Qi Deng, Ke-Yu Sun, Le Chi, Shaopeng Yang, Zhiguang Wang, Jun Xin, Hong-Bo Wang, Xiaoqun Ji, Guangju |
| description | Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca
2+
dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca
2+
leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment. |
| doi_str_mv | 10.1038/srep21087 |
| format | Article |
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2+
dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca
2+
leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep21087</identifier><identifier>PMID: 26888649</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 14/19 ; 14/34 ; 631/378/1595/1554 ; 64/110 ; 64/60 ; 692/617/375 ; 9/30 ; Animals ; Apoptosis ; Calcium (intracellular) ; Calcium channels ; Calcium currents ; Cognitive ability ; Excitability ; Hippocampus ; Hippocampus - cytology ; Hippocampus - metabolism ; Humanities and Social Sciences ; Leak channels ; Learning ; Long term memory ; Long-term potentiation ; Long-Term Potentiation - physiology ; Macromolecules ; Maze Learning - physiology ; Memory ; Memory - physiology ; Mice ; Mice, Knockout ; multidisciplinary ; Post traumatic stress disorder ; Potassium currents ; Rodents ; Ryanodine receptors ; Science ; Tacrolimus ; Tacrolimus Binding Proteins - genetics ; Tacrolimus Binding Proteins - metabolism ; Tacrolimus-binding protein</subject><ispartof>Scientific reports, 2016-02, Vol.6 (1), p.21087-21087, Article 21087</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Feb 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-6b438a547eabd9a8243873ce00e8772597f81bc1b43f09ed291dc77e4bf41ee83</citedby><cites>FETCH-LOGICAL-c438t-6b438a547eabd9a8243873ce00e8772597f81bc1b43f09ed291dc77e4bf41ee83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758079/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758079/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26888649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Qi</creatorcontrib><creatorcontrib>Deng, Ke-Yu</creatorcontrib><creatorcontrib>Sun, Le</creatorcontrib><creatorcontrib>Chi, Shaopeng</creatorcontrib><creatorcontrib>Yang, Zhiguang</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Xin, Hong-Bo</creatorcontrib><creatorcontrib>Wang, Xiaoqun</creatorcontrib><creatorcontrib>Ji, Guangju</creatorcontrib><title>Calstabin 2: An important regulator for learning and memory in mice</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca
2+
dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca
2+
leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment.</description><subject>13/2</subject><subject>13/31</subject><subject>14/19</subject><subject>14/34</subject><subject>631/378/1595/1554</subject><subject>64/110</subject><subject>64/60</subject><subject>692/617/375</subject><subject>9/30</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Calcium (intracellular)</subject><subject>Calcium channels</subject><subject>Calcium currents</subject><subject>Cognitive ability</subject><subject>Excitability</subject><subject>Hippocampus</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Leak channels</subject><subject>Learning</subject><subject>Long term memory</subject><subject>Long-term potentiation</subject><subject>Long-Term Potentiation - physiology</subject><subject>Macromolecules</subject><subject>Maze Learning - physiology</subject><subject>Memory</subject><subject>Memory - 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cytology</topic><topic>Hippocampus - metabolism</topic><topic>Humanities and Social Sciences</topic><topic>Leak channels</topic><topic>Learning</topic><topic>Long term memory</topic><topic>Long-term potentiation</topic><topic>Long-Term Potentiation - physiology</topic><topic>Macromolecules</topic><topic>Maze Learning - physiology</topic><topic>Memory</topic><topic>Memory - physiology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>multidisciplinary</topic><topic>Post traumatic stress disorder</topic><topic>Potassium currents</topic><topic>Rodents</topic><topic>Ryanodine receptors</topic><topic>Science</topic><topic>Tacrolimus</topic><topic>Tacrolimus Binding Proteins - genetics</topic><topic>Tacrolimus Binding Proteins - metabolism</topic><topic>Tacrolimus-binding protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Qi</creatorcontrib><creatorcontrib>Deng, Ke-Yu</creatorcontrib><creatorcontrib>Sun, Le</creatorcontrib><creatorcontrib>Chi, Shaopeng</creatorcontrib><creatorcontrib>Yang, Zhiguang</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Xin, Hong-Bo</creatorcontrib><creatorcontrib>Wang, Xiaoqun</creatorcontrib><creatorcontrib>Ji, Guangju</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>ProQuest Biological Science Journals</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Qi</au><au>Deng, Ke-Yu</au><au>Sun, Le</au><au>Chi, Shaopeng</au><au>Yang, Zhiguang</au><au>Wang, Jun</au><au>Xin, Hong-Bo</au><au>Wang, Xiaoqun</au><au>Ji, Guangju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calstabin 2: An important regulator for learning and memory in mice</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-02-18</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>21087</spage><epage>21087</epage><pages>21087-21087</pages><artnum>21087</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca
2+
dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca
2+
leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26888649</pmid><doi>10.1038/srep21087</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Nature Open Access; SpringerOpen; MEDLINE; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | 13/2 13/31 14/19 14/34 631/378/1595/1554 64/110 64/60 692/617/375 9/30 Animals Apoptosis Calcium (intracellular) Calcium channels Calcium currents Cognitive ability Excitability Hippocampus Hippocampus - cytology Hippocampus - metabolism Humanities and Social Sciences Leak channels Learning Long term memory Long-term potentiation Long-Term Potentiation - physiology Macromolecules Maze Learning - physiology Memory Memory - physiology Mice Mice, Knockout multidisciplinary Post traumatic stress disorder Potassium currents Rodents Ryanodine receptors Science Tacrolimus Tacrolimus Binding Proteins - genetics Tacrolimus Binding Proteins - metabolism Tacrolimus-binding protein |
| title | Calstabin 2: An important regulator for learning and memory in mice |
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