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ERIC Number: EJ916894
Record Type: Journal
Publication Date: 2011-Jan
Pages: 9
Abstractor: As Provided
Reference Count: 0
ISBN: N/A
ISSN: ISSN-1072-0502
The Anaphase Promoting Complex Is Required for Memory Function in Mice
Kuczera, Tanja; Stilling, Roman Manuel; Hsia, Hung-En; Bahari-Javan, Sanaz; Irniger, Stefan; Nasmyth, Kim; Sananbenesi, Farahnaz; Fischer, Andre
Learning & Memory, v18 n1 p49-57 Jan 2011
Learning and memory processes critically involve the orchestrated regulation of de novo protein synthesis. On the other hand it has become clear that regulated protein degradation also plays a major role in neuronal plasticity and learning behavior. One of the key pathways mediating protein degradation is proteosomal protein destruction. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets proteins for proteosomal degradation by the 26S proteasome. While the APC/C is essential for cell cycle progression it is also expressed in postmitotic neurons where it has been implicated with axonal outgrowth and neuronal survival. In this study we addressed the role of APC/C in learning and memory function by generating mice that lack the essential subunit APC2 from excitatory neurons of the adult forebrain. Those animals are viable but exhibit a severe impairment in the ability to extinct fear memories, a process critical for the treatment of anxiety diseases such as phobia or post-traumatic stress disorder. Since deregulated protein degradation and APC/C activity has been implicated with neurodegeneration we also analyzed the effect of "Apc2" deletion in a mouse model for Alzheimer's disease. In our experimental setting loss of APC2 form principle forebrain neurons did not affect the course of pathology in an Alzheimer's disease mouse model. In conclusion, our data provides genetic evidence that APC/C activity in the adult forebrain is required for cognitive function.
Cold Spring Harbor Laboratory Press. 500 Sunnyside Boulevard, Woodbury, NY 11797-2924. Tel: 800-843-4388; Tel: 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://www.learnmem.org/
Publication Type: Journal Articles; Reports - Evaluative
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A