The central hypothesis of this proposal is that neurons sense the lengths of the axonal microtubule cytoskeleton on an ongoing basis by bidirectional motor-dependent axon-nucleus communication, and that the oscillating retrograde signal
generated by this mechanism provides input for the coordinated regulation of neuronal biosynthesis and axonal growth.
2001) Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors.
2001) Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals.
2013) Changing the tune: plasticity and adaptation of retrograde signals.
Although the capture of 24-h LTF is independent of protein synthesis, the initiation of LTF by synaptic application of 5-HT is dependent on protein synthesis, suggesting that the newly synthesized local proteins may serve as, or help generate, the presumed retrograde signal to the nucleus.
If the retrograde signal induced expression (or repression) of new macromolecules in the soma that were subsequently shipped to the synapse, additional time might be required for these intermediate steps.
However, if in our experiments LTF triggered by synaptic application of 5-HT to distal terminals requires retrograde transport to the soma and subsequent somatic protein synthesis, then one might have expected that protein synthesis in the soma could have returned to normal by the time the retrograde signal arrived, and hence LTF blockade might not have occurred.
ProPlantStress will employ these approaches, which I co-developed during my postdoctoral research, to two linked abiotic and biotic stress conditions: i) Time-resolved mapping of chloroplast protein processing induced by high intensity light will reveal novel mechanisms of retrograde signal
transduction, stress response and acclimation; ii) Profiling of protein processing triggered by pathogen recognition, combined with substrate identification for selected host and bacterial pathogen effector proteases will identify proteins with novel functions in plant immune responses and systemic signaling.
In cases where the retrograde messenger is not sufficient, pairing the other factor(s) with the retrograde signal
should mimic the phenomenon.
This result implies that a retrograde signal is necessary for the long-term presynaptic morphological changes.
Given this situation, it is clear that these changes must be mediated by some, as yet unknown, retrograde signal.
During my PhD and postdoctoral research, we have shown that a retrograde signal
generated in the chloroplast by light modulates alternative splicing.