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Citation
Walker, J.A., Tchoudakova, A.V., McKenney, P.T., Brill, S., Wu, D., Cowley, G.S., Hariharan, I.K., Bernards, A. (2006). Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons.  Genes Dev. 20(23): 3311--3323.
FlyBase ID
FBrf0193208
Publication Type
Research paper
Abstract

Neurofibromatosis type 1 (NF1) is among the most common genetic disorders of humans and is caused by loss of neurofibromin, a large and highly conserved protein whose only known function is to serve as a GTPase-Activating Protein (GAP) for Ras. However, most Drosophila NF1 mutant phenotypes, including an overall growth deficiency, are not readily modified by manipulating Ras signaling strength, but are rescued by increasing signaling through the cAMP-dependent protein kinase A pathway. This has led to suggestions that NF1 has distinct Ras- and cAMP-related functions. Here we report that the Drosophila NF1 growth defect reflects a non-cell-autonomous requirement for NF1 in larval neurons that express the R-Ras ortholog Ras2, that NF1 is a GAP for Ras1 and Ras2, and that a functional NF1-GAP catalytic domain is both necessary and sufficient for rescue. Moreover, a Drosophila p120RasGAP ortholog, when expressed in the appropriate cells, can substitute for NF1 in growth regulation. Our results show that loss of NF1 can give rise to non-cell-autonomous developmental defects, implicate aberrant Ras-mediated signaling in larval neurons as the primary cause of the NF1 growth deficiency, and argue against the notion that neurofibromin has separable Ras- and cAMP-related functions.

PubMed ID
PubMed Central ID
PMC1686607 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genes Dev.
    Title
    Genes & Development
    Publication Year
    1987-
    ISBN/ISSN
    0890-9369
    Data From Reference
    Aberrations (2)
    Alleles (65)
    Genes (25)
    Human Disease Models (1)
    Physical Interactions (2)
    Natural transposons (1)
    Insertions (14)
    Experimental Tools (3)
    Transgenic Constructs (31)
    Transcripts (3)