REQUIREMENT OF DROSOPHILA NF1 FOR ACTIVATION OF ADENYLYL-CYCLASE BY PACAP38-LIKE NEUROPEPTIDES

The human neurofibromatosis type 1 (NF1) tumor suppressor protein func tions as a Ras-specific guanosine triphosphatase-activating protein, b ut the identity of Ras-mediated pathways modulated by NF1 remains unkn own. A study of Drosophila NF1 mutants revealed that NF1 is essential for the cellular response to the neuropeptide PACAP38 (pituitary adeny lyl cyclase-activating polypeptide) at the neuromuscular junction, The peptide induced a 100-fold enhancement of potassium currents by activ ating the Ras-Raf and adenylyl cyclase-adenosine 3',5'-monophosphate ( cAMP) pathways, This response was eliminated in NF1 mutants, NF1 appea rs to regulate the rutabaga-encoded adenylyl cyclase rather than the R as-Raf pathway, Moreover, the NF1 defect was rescued by the exposure o f cells to pharmacological treatment that increased concentrations of cAMP.