BMP signaling is determined by the composition, oligomerisation and lateral mobility of BMP receptors at the plasma membrane. Our preliminary work suggests that spatial segregation of distinct signaling routes is achieved by SEPT9 scaffolds and thereby important for cell fate decisions. The overall goal of project A20 is to understand the molecular basis for the septin-scaffold in the spatial and functional organization of BMP2 signaling by (1) characterizing the molecular mechanism and composition of SEPT9/BMP receptor and SEPT9/Smad interactions, (2) studying the lateral mobility of BMP receptors in a SEPT9 context using single molecule tracking, and (3) by investigating the impact of SEPT9 scaffolds on the functional outcome of BMP signaling.
Hiepen, C., Benn, A., Denkis, A., Lukonin, I., Weise, C., Boergermann, J. H., and Knaus, P. BMP2-induced chemotaxis requires PI3K p55gamma/p110alpha-dependent phosphatidylinositol (3,4,5)-triphosphate production and LL5beta recruitment at the cytocortex. BMC Biol. 12, 43 (2014).
Guzman, A., Zelman-Femiak, M., Boergermann, J. H., Paschkowsky, S., Kreuzaler, P. A., Fratzl, P., Harms, G. S., and Knaus, P. SMAD versus non-SMAD signaling is determined by lateral mobility of bone morphogenetic protein (BMP) receptors. Journal of Biological Chemistry 287, 39492–39504 (2012).
Ewers, H., Römer, W., Smith, A. E., Bacia, K., Dmitrieff, S., Chai, W., Mancini, R., Kartenbeck, J., Chambon, V., Berland, L., Oppenheim, A., Schwarzmann, G., Feizi, T., Schwille, P., Sens, P., Helenius, A., and Johannes, L. GM1 structure deter-mines SV40-induced membrane invagination and infection. Nat Cell Biol 12, 11–8 (2010).
Ries, J., Kaplan, C., Platonova, E., Eghlidi, H and Ewers, H. A simple, versatile method for GFP-based super-resolution microscopy via nanobodies. Nat Methods 9, 582–584 (2012).
Ewers, H., Jacobsen, V., Klotzsch, E., Smith, A. E., Helenius, A., and Sandoghdar, V. Label-free optical detection and tracking of single virions bound to their receptors in supported membrane bilayers. Nano Lett 7, 2263–2266 (2007).
Schoen, I., Ries, J., Klotzsch, E., Vogel, V., and Ewers, H. Binding-Activated Localization Microscopy of DNA Structures. Nano Lett 11, 4008-11 (2011).
Ewers, H., Tada, T, Petersen, J. D., Racz, B., Sheng, M., and Choquet, D. A septin-dependent diffusion barrier at dendritic spine necks (in press) PLoS One. doi10.1371/journal.pone.0113916
Bagarova, J., Vonner, A. J., Armstrong, K. A., Börgermann, J., Lai, C. S. C., Deng, D. Y., Beppu, H., Alfano, I., Filippakopoulos, P., Morrell, N. W., Bullock, A. N., Knaus, P., Mishina, Y., and Yu, P. B. Constitutively active ALK2 receptor mutants require type II receptor cooperation. Mol Cell Biol 33, 2413–2424 (2013).
Schwappacher, R., Weiske, J., Heining, E., Ezerski, V., Marom, B., Henis, Y. I., Huber, O., and Knaus, P. Novel crosstalk to BMP signalling: cGMP-dependent kinase I modulates BMP receptor and Smad activity. EMBO J 28, 1537–1550 (2009).
Sieber, C., Kopf, J., Hiepen, C., and Knaus, P. Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev. 20, 343–355 (2009).