Blots were revealed with enhanced chemiluminescent reagents

GFRs. We are not aware of other descriptions of nuclear localization of FGFRs in invertebrates, but this phenomenon has been described in cultured fibroblasts and in human astrocytes and glioma cells, where nuclear localization appears to be correlated with transcriptional regulation and subsequent glial-cell proliferation. Further work is needed to determine whether or not nuclear localization of FGFRs can be connected to specific cellular functions in invertebrates. Heartless expression also has been reported in embryonic Drosophila neurons grown in culture and in vivo. We likewise saw evidence of FGFRs in the AL neurons, but only in their cell bodies, not in their dendrites or axons. There is evidence that FGFRs can be imported directly from endoplasmic reticulum to the nucleus without ever being expressed on the plasma membrane. This latter phenomenon, termed “integrative nuclear FGFR signaling”may be relevant to our observation that FGFR labeling in the AL neurons is limited to their cell bodies, and might help explain why AL GS-1101 custom synthesis neuron cell bodies in PD173074-treated animals continue to label for activated FGFRs. In this scenario, activation of signaling pathways within AL neurons would lead to direct translocation of FGFRs from the endoplasmic reticulum to the nucleus in order to modulate gene transcription. The nature of the role of FGFRs in AL neurons remains unanswered. Heparan sulfate proteoglycans have been described as essential co-receptors for FGFs. As was the case for pFGFRs, we found HSPGs expressed in glial cells and AL neurons. Additionally, we found HSPGs both on cell processes and in nuclei. This, too, is in agreement with published accounts that HSPG localization can vary. We have shown previously that ORNs express EGFRs and find here that these EGFRs are activated ” normally following treatment with PD173074. If ORN EGFR activation had been blocked, ORN axons would have stalled in the sorting zone, making it thicker than normal. The fact that antennal lobes of control and treated animals display 10411607” sorting zones of comparable diameter indicates that ORN axons did not stall in the sorting zone, as they do when EGFR activation is blocked with PD168393. This supports the conclusion that PD173074 does not block EGFR activation in M. sexta. We lack an antibody for the activated form of the only other Manduca receptor tyrosine kinase characterized to date, the Eph receptor, so we could not check for its possible inactivation. However, PD173074 was designed to competitively bind to the Glial FGFRs in Glia-Neuron Signaling ATP-binding pocket of the FGF receptor, and amino acid alignments show that the Eph receptor lacks 8 of the 18 amino acids at specific locations needed to form the binding pocket for PD173074. Thus PD173074 appears an unlikely candidate for binding to and blocking activation of the Eph receptor.Because it was important to determine whether the altered fasciculation of ORNs traversing the sorting zone in PD173074treated animals was a direct result of blocking ORN FGFR activation, we also looked for evidence of expression of FGFRs by olfactory receptor neurons. We found no evidence for pFGFRs in ORN cell bodies, axons, or dendrites within antennal sensilla, suggesting that the altered behavior of ORN axons in the sorting zone is the consequence of interrupting an interaction between the ORNs and glial cells that depends on FGFR activation in the glial cells. Glial FGFRs in Glia-Neuron Signaling Blocking glial FGFR