Barry Knox, PhD
Now is a very exciting time in our department. With the advent of new imaging and molecular techniques, scientific doors that were previously closed have been flung wide open. Read more...
Research Highlight: Stk25 as a modifier of Reelin Dab1 signaling
The Howell Lab
The Reelin-Dab1 signaling pathway regulates neuronal positioning and dendritogenesis in the developing nervous system. Although details are emerging about the signaling cascade itself, the early cell biological changes that influence these phenomena are poorly understood. The Howell lab recently identified Stk25 as a modifier of Reelin Dab1 signaling and showed that it regulates neuronal polarization as part of the LKB1-STRAD pathway.
Knocking down Stk25 hinders axon formation in nascent neurons, whereas overexpressing it leads to the production of multiple axons (Matsuki et al., 2010). Furthermore, dab1 mutant neurons are found to produce multiple axons, in vitro, in an Stk25 expression level-dependent manner. Stk25 has previously been shown to interact with the Golgi shaping protein GM130 (Preisinger et al., 2004). Reducing expression of Stk25, LKB1 or GM130 leads to Golgi fragmentation, while Stk25 overexpression rescues the Stk25 and LKB1 but not the GM130 knockdown phenotypes. This suggests that Stk25 may act on a signal transduction pathway between LKB1 and GM130.
Interestingly, Dr. Matsuki also found that the Reelin-Dab1 signaling pathway regulates Golgi morphology (Matsuki et al., 2010). Reelin-conditioned media (CM) stimulation of hippocampal pyramidal neurons results in the deployment of the Golgi apparatus into dendrites compared to control-CM treatment, which does not (upper panel of figure). Stk25 overexpression suppresses this phenomenon. Since the position of Golgi has previously been shown to regulate the size and branching of proximal dendrites (Ye et al., 2007), the Howell lab is interested to determine if Reelin-Dab1 signaling regulates dendritic asymmetry through the regulation of Golgi deployment.
In summary, the cell polarity and Golgi deployment regulating activities of the Reelin-Dab1 signaling pathway are balanced by the expression of Stk25, which plays a role on the LKB1-STRAD pathway (lower panel of figure). It remains to be determined how these pathways converge to influence these biological processes.
Matsuki, T., Matthews, R.T., Cooper, J.A., van der Brug, M.P., Cookson, M.R., Hardy, J.A., Olson, E.C., and Howell, B.W. (2010). Reelin and stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment. Cell 143, 826-836.
Preisinger, C., Short, B., De Corte, V., Bruyneel, E., Haas, A., Kopajtich, R., Gettemans, J., and Barr, F.A. (2004). YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta. J Cell Biol 164, 1009-1020.
Ye, B., Zhang, Y., Song, W., Younger, S.H., Jan, L.Y., and Jan, Y.N. (2007). Growing dendrites and axons differ in their reliance on the secretory pathway. Cell 130, 717-729.