Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation

Ho, I. S., Hannan, F., Guo, H.-F., Hakker, I., Zhong, Y. (June 2007) Distinct functional domains of neurofibromatosis type 1 regulate immediate versus long-term memory formation. J Neurosci, 27 (25). pp. 6852-7. ISSN 1529-2401 (Electronic)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/17581973
DOI: 10.1523/jneurosci.0933-07.2007

Abstract

Neurofibromatosis type 1 (NF1) is a dominant genetic disorder that causes tumors of the peripheral nervous system. In addition, >40% of afflicted children have learning difficulties. The NF1 protein contains a highly conserved GTPase-activating protein domain that inhibits Ras activity, and the C-terminal region regulates cAMP levels via G-protein-dependent activation of adenylyl cyclase. Behavioral analysis indicates that learning is disrupted in both Drosophila and mouse NF1 models. Our previous work has shown that defective cAMP signaling leads to the learning phenotype in Drosophila Nf1 mutants. In the present report, our experiments showed that in addition to learning, long-term memory was also abolished in Nf1 mutants. However, altered NF1-regulated Ras activity is responsible for this defect rather than altered cAMP levels. Furthermore, by expressing clinically relevant human NF1 mutations and deletions in Drosophila Nf1-null mutants, we demonstrated that the GAP-related domain of NF1 was necessary and sufficient for long-term memory, whereas the C-terminal domain of NF1 was essential for immediate memory. Thus, we show that two separate functional domains of the same protein can participate independently in the formation of two distinct memory components.

Item Type: Paper
Uncontrolled Keywords: Animals Drosophila Drosophila Proteins/chemistry/genetics/ physiology Humans Memory/physiology Memory, Short-Term/ physiology Mutation Nerve Tissue Proteins/chemistry/genetics/ physiology Neurofibromin 1/chemistry/genetics/ physiology Protein Structure, Tertiary/genetics Retention (Psychology)/ physiology ras GTPase-Activating Proteins/chemistry/genetics/ physiology neurofibromatosis type 1 long-term memory learning Drosophila cognitive disorder human disease
Subjects: diseases & disorders > cancer
diseases & disorders > congenital hereditary genetic diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NF1
diseases & disorders > congenital hereditary genetic diseases > neurofibromatosis
CSHL Authors:
Communities: CSHL labs > Zhong lab
Depositing User: CSHL Librarian
Date: 20 June 2007
Date Deposited: 15 Nov 2011 15:56
Last Modified: 27 Mar 2018 19:11
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23034

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