The Cell Migration Gateway has a report up on the recent Mechanisms of Chemotaxis, 93rd Boehringer Ingelheim Fonds International Titisee Conference, detailing a number of the important themes which emerged during conference sessions.
Among the interesting highlights that the CMG mentions (below the fold):
- In her keynote lecture, Cori Bargmann (The Rockefeller University, New York), described the molecular mechanisms underlying the response of C. elegans to different odours. Thanks to the relatively simple nervous system of the nematode, the specific neurons that generate movement towards or away from certain stimuli have been defined, thus facilitating the determination of the signalling components involved. As in other animals, odours are detected by G protein-coupled odorant receptors, which lead to the activation of guanylyl cyclases and an increase in intracellular calcium. Interestingly, the Bargmann laboratory have also found a role for glutamatergic signalling in modulating the response to particular sensory inputs, and for serotonin in avoiding noxious foods. In humans, an increase in serotonin release from enterochromaffin cells has been associated with causing nausea during chemotherapy, suggesting a conserved role for serotonin in the communication between the intestine and the nervous system.
- The ability of D. discoideum, a soil amoeba, to move up a gradient of an attractive chemical and form aggregates is crucial for their survival in harsh environmental conditions. Rick Firtel’s talk (University of California, La Jolla) focused on the signalling feedback loops that amplify shallow extracellular gradients into steep intracellular ones. Work from his lab, and others, has shown that local activation of Ras stimulates phosphatidylinositol 3-kinase (PI3K). This leads to the activation of Rac and actin polymerization, which in turn leads to the recruitment of more PI3K and Rac guanine nucleotide exchange factors (GEFs) thus establishing a positive feedback loop at the leading edge that ensures directional cell movement. By knocking out three PI3Ks in D. discoideum, Firtel’s group significantly impaired directional movement as the cells were unable to form stable pseudopods.
- The last session of the meeting focussed on nerve cell chemotropism. During the development of the nervous system, neurons migrate and extend neurites towards their synaptic targets. The leading edge of the axon, or growth cone, functions as an exquisite sensor that detects and responds to both attractive and repulsive cues that help guide axons to their destinations. Rüdiger Klein (Max-Planck Institute for Neurobiology, Munich-Martinsried) presented work on the Eph family of tyrosine kinase receptors and ephrins, well established guidance molecules in the retina and spinal cord. Interestingly, reminiscent of data on bacterial chemotaxis, ephrin-induced Eph receptor clustering into higher order aggregates affects the local signalling output and thereby, guidance decisions.
- James Zheng (University of Medicine and Dentistry, New Jersey) showed how asymmetric elevations of calcium in growth cones regulate axon turning. Interestingly, the actual levels of calcium determine whether the growth cone turns towards or away from a guidance cue. Examination of attractive turning induced by brain-derived neurotrophic factor (BDNF), or local uncaging of calcium, reveals that both Src tyrosine kinase activation and local synthesis of β-actin are required for the turning response.