Journal
NATURE NEUROSCIENCE
Volume 16, Issue 9, Pages 1248-U124Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3474
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Funding
- UK Medical Research Council Career Establishment Grant [MRCG0200140]
- Wellcome Trust [WT094175/Z/10/Z]
- Wellcome Trust equipment grant [WT073228/Z/03/Z]
- Wellcome Trust programme grant [WT081744MA]
- European Union Marie Curie International Incoming Fellowship [PIIF-GA-2010-274193-NPN]
- UK Medical Research Council studentship
- Brunei government studentship
- Medical Research Council [G0200140, G1000133] Funding Source: researchfish
- Wellcome Trust [100321/Z/12/Z] Funding Source: researchfish
- MRC [G1000133] Funding Source: UKRI
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Neurotrophin receptors corresponding to vertebrate Trk, p75(NTR) or Sortilin have not been identified in Drosophila, thus it is unknown how neurotrophism may be implemented in insects. Two Drosophila neurotrophins, DNT1 and DNT2, have nervous system functions, but their receptors are unknown. The Toll receptor superfamily has ancient evolutionary origins and a universal function in innate immunity. Here we show that Toll paralogs unrelated to the mammalian neurotrophin receptors function as neurotrophin receptors in fruit flies. Toll-6 and Toll-7 are expressed in the CNS throughout development and regulate locomotion, motor axon targeting and neuronal survival. DNT1 (also known as NT1 and spz2) and DNT2 (also known as NT2 and spz5) interact genetically with Toll-6 and Toll-7, and DNT1 and DNT2 bind to Toll-6 and Toll-7 promiscuously and are distributed in vivo in domains complementary to or overlapping with those of Toll-6 and Toll-7. We conclude that in fruit flies, Tolls are not only involved in development and immunity but also in neurotrophism, revealing an unforeseen relationship between the neurotrophin and Toll protein families.
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