Isoform‐specific knockout of <i>FE65</i> leads to impaired learning and memory

Wang, Baiping; Hu, Qubai; Hearn, Mark G.; Shimizu, Kimiko; Ware, Carol B.; Liggitt, Dennis H.; Jin, Lee Way; Cool, Bethany H.; Storm, Daniel R.; Martin, George M.

doi:10.1002/jnr.10834

Cited by 62 publications

(106 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1E) were comparable between WT and p97FE65 À/À mice. These data, together with a previous report (Wang et al 2004a), implicate that there is no severe abnormality in hippocampal morphology in p97FE65 À/À mice.…”

Section: Results P97fe65 à/à Mice Show Normal Hippocampus Formationsupporting

confidence: 85%

“…FE65 is predominately neurospecific and is expressed in the hippocampus (Kesavapany et al 2002;Wang et al 2004a), a brain region involved in certain forms of learning and memory. The gene was first identified as an interaction protein of the b-amyloid precursor protein (APP) (Fiore et al 1995).…”

mentioning

confidence: 99%

“…Correlated with the phenotypes in APP KO mice, defective hippocampus-dependent memories have been observed with isoform-specific p97FE65 À/À mice, which express only p60FE65 (p60), but not p97FE65 (Wang et al 2004a). p97 and p60 are possibly generated by alternative translation from the same transcript (Wang et al 2004a;B Cool, G Zitnik, G Martin, and Q Hu, unpubl.).…”

mentioning

confidence: 99%

“…p97 and p60 are possibly generated by alternative translation from the same transcript (Wang et al 2004a;B Cool, G Zitnik, G Martin, and Q Hu, unpubl.). p60 is the shorter version of p97, lacks part of the WW domain, and is incapable of activating gene expression (B Cool, G Zitnik, G Martin, and Q Hu, unpubl.).…”

mentioning

confidence: 99%

See 3 more Smart Citations

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

Wang¹,

Zhang²,

Moon³

et al. 2009

Learn. Mem.

Self Cite

View full text Add to dashboard Cite

FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of b-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65 À/À ) mice. When examined using the Morris water maze, p97FE65 À/À mice were impaired for the hidden platform task but showed normal performance in the probe test. To further discriminate the role of FE65 in acquisition and memory consolidation, we examined p97FE65 À/À mice with temporal dissociative passive avoidance (TDPA) and contextual fear conditioning (CFC). p97FE65 À/À mice showed impaired shortterm memory for both TDPA and CFC when tested 10 min after training. After multiple TDPA training sessions, the crossover latency of some p97FE65 À/À mice reached the cutoff value, but it significantly decayed in 8 d. At the Schaffer collateral-CA1 synapses, p97FE65 À/À mice showed defective early-phase LTP (E-LTP). These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.

show abstract

Section: Results P97fe65 à/à Mice Show Normal Hippocampus Formationsupporting

confidence: 85%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

Wang¹,

Zhang²,

Moon³

et al. 2009

Learn. Mem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, they show learning and memory impairment and defective early-phase LTP at the Shaffer collateral-CA1 synapses (28). Moreover, Fe65 null mice show enhanced neurogenesis (29), similar to that observed in APP2/2 mice, as well as a slight increase of GnRH-1 neurons during development (30).…”

Section: The Phenotype Of Fe65 Null Animalsmentioning

confidence: 59%

Fe65 matters: New light on an old molecule

et al. 2012

View full text Add to dashboard Cite

SummaryThe discovery that the main constituents of amyloid deposits, characteristic of Alzheimer neuropathology, derive from the proteolytic processing of the membrane precursor amyloid precursor protein (APP) is one of the milestones of the research history of this disease. Despite years of intense studies, the functions of APP and of its amyloidogenic processing are still under debate. One focus of these studies was the complex network of protein-protein interactions centered at the cytosolic domain of APP, which suggests the involvement of APP in a lively signaling pathway. Fe65 was the first protein to be demonstrated to interact with the APP cytodomain. Starting from this observation, a large body of data has been gathered, indicating that Fe65 is an adaptor protein, which binds numerous proteins, further than APP. Among these proteins, the crosstalk with Mena, mDab, and Abl suggested the involvement of the Fe65-APP complex in the regulation of cell motility, with a relevant role in differentiation and development. Other partners, like the histone acetyltransferase Tip60, indicated the possibility that the nuclear fraction of Fe65 could be involved in gene regulation and/or DNA repair.2012 IUBMB IUBMB Life, 64(12): 936-942, 2012

show abstract

Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1

Chan

Chai

et al. 2010

J of Cellular Biochemistry

View full text Add to dashboard Cite

FE65 is a neuronal-enriched adaptor protein that binds to the Alzheimer's disease amyloid precursor protein (APP). FE65 forms a transcriptionally active complex with the APP intracellular domain (AICD). The precise gene targets for this complex are unclear but several Alzheimer's disease-linked genes have been proposed. Additionally, evidence suggests that FE65 influences APP metabolism. The mechanism by which FE65 expression is regulated is as yet unknown. To gain insight into the regulatory mechanism, we cloned a 1.6 kb fragment upstream of the human FE65 gene and found that it possesses particularly strong promoter activity in neurones. To delineate essential regions in the human FE65 promoter, a series of deletion mutants were generated. The minimal FE65 promoter was located between -100 and +5, which contains a functional Sp1 site. Overexpression of the transcription factor Sp1 potentiates the FE65 promoter activity. Conversely, suppression of the FE65 promoter was observed in cells either treated with an Sp1 inhibitor or in which Sp1 was knocked down. Furthermore, reduced levels of Sp1 resulted in downregulation of endogenous FE65 mRNA and protein. These findings reveal that Sp1 plays a crucial role in transcriptional control of the human FE65 gene.

show abstract

Isoform‐specific knockout of FE65 leads to impaired learning and memory

Cited by 62 publications

References 46 publications

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

Fe65 matters: New light on an old molecule

Transcriptional regulation of human FE65, a ligand of Alzheimer's disease amyloid precursor protein, by Sp1

Contact Info

Product

Resources

About