A neurofibromatosis-1-regulated pathway is required for learning in Drosophila.

Abstract	The tumour-suppressor gene Neurofibromatosis 1 (Nf1) encodes a Ras-specific GTPase activating protein (Ras-GAP). In addition to being involved in tumour formation, NF1 has been reported to cause learning defects in humans and Nf1 knockout mice. However, it remains to be determined whether the observed learning defect is secondary to abnormal development. The Drosophila NF1 protein is highly conserved, showing 60% identity of its 2,803 amino acids with human NF1 (ref. 12). Previous studies have suggested that Drosophila NF1 acts not only as a Ras-GAP but also as a possible regulator of the cAMP pathway that involves the rutabaga (rut)-encoded adenylyl cyclase. Because rut was isolated as a learning and short-term memory mutant, we have pursued the hypothesis that NF1 may affect learning through its control of the Rut-adenylyl cyclase/cAMP pathway. Here we show that NF1 affects learning and short-term memory independently of its developmental effects. We show that G-protein-activated adenylyl cyclase activity consists of NF1-independent and NF1-dependent components, and that the mechanism of the NF1-dependent activation of the Rut-adenylyl cyclase pathway is essential for mediating Drosophila learning and memory.
Authors	H F Guo, J Tong, F Hannan, L Luo, Y Zhong
Journal	Nature (Nature) Vol. 403 Issue 6772 Pg. 895-8 (Feb 24 2000) ISSN: 0028-0836 [Print] England
PMID	10706287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Drosophila Proteins Insect Proteins NF1 protein, Drosophila Nerve Tissue Proteins ras GTPase-Activating Proteins Cyclic AMP GTP-Binding Proteins Adenylyl Cyclases Calcium
Topics	Adenylyl Cyclases (genetics, metabolism) Animals Animals, Genetically Modified Calcium (metabolism) Conditioning, Classical Cyclic AMP (metabolism) Drosophila (genetics, physiology) Drosophila Proteins Electric Stimulation Enzyme Activation GTP-Binding Proteins (metabolism) Heat-Shock Response Insect Proteins (genetics, physiology) Learning (physiology) Memory, Short-Term (physiology) Mutation Nerve Tissue Proteins Smell (physiology) ras GTPase-Activating Proteins (genetics, physiology)

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