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Functional Analysis of Human NF1 in Drosophila

机译：人类NF1在果蝇中的功能分析

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Neurofibromatosis type 1 (NF1) is a common single gene neurogenetic disorder characterized by tumors in peripheral nerve terminals. A large fraction of patients also have learning problem. Such learning phenotypes have been recapitulated in animal models, including in mouse and Drosophila mutants. This proposal mainly examines functions of the neurofibromatosis type 1 (NF1) gene and its regulated signal transduction pathways in learning and memory in Drosophila. We have reported in previous annual report that the NF1 C-terminal mediating Gsalpha/NF1-dependent activation of adenylyl cyclase (AC) and the GAP- related domain (GRD) for regulating Ras activity, such as Ras/NF1-dependent AC activation. Over last funding period, we mainly focused on studying roles of these two distinct functional domains in learning and memory. Our study revealed that both immediate memory and long-term memory (LTM) are abnormal in NF1 mutants. Our analysis of effects of clinically relevant mutant NF1 genes concluded that LTM formation only requires GAP function of NF1 and is mediate by the GRD while immediate memory only involves the C-terminal. Thus, NF1 is required for formation of two memory components but through distinct functional domains that regulates different signal transduction pathways. Moreover, a spatial and temporal analysis revealed a role of NF1 in learning and LTM in distinct brain regions and at the LTM retrieval, but not in memory formation or consolidation.

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