A17 - Protein scaffolds in synaptic endomembrane degradation

Principal Investigator

Prof. Dr. Robin Hiesinger, FU Berlin

It is unclear how synapses are kept functional over long periods of time despite a high level of local membrane turnover (Fig. 1). To identify protein scaffolds that regulate this process, we have recently performed a systematic functional profiling of all Rab GTPases in neurons in Drosophila. Rab GTPases act as switches for the assembly of protein scaffolds in the endomembrane system. In this proposal we will elucidate neuron-specific protein machinery including the novel Rab GTPases Rab26 and RabX4 which regulate at least one neuron-specific SNARE protein (neuronal Synaptobrevin) and a neuron-specific v-ATPase subunit (V100) (Fig. 2). The goal of this proposal is to identify and characterize the Rab-based protein scaffolds that control degradation in the neuronal endomembrane system.

 Figure 1


Figure 2


References:

  • Langen, M.*, Agi, E.*, Altschuler, D., Wu, L.*, Altschuler, S.*, and Hiesinger, P.R.* (2015) The Developmental Rules of Neural Superposition. Cell162(1):120-33

  • Wang, D., Epstein, D., Khalaf, O., Srinivasan, S., Williamson, W.R., Fayyazuddin, A., Quiocho, F.A., and Hiesinger, P.R. (2014). Calcium/Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1. J. Cell. Biol. 205(1):21-31.

  • Cherry, S., Jin, E.J., Ozel, M.N., Lu, Z., Agi, E., Wang, D., Meinertzhagen, I.A., Chan, C.-C., and Hiesinger, P.R. 2013. Charcot-Maire-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function. eLife2(0):e01064

  • Haberman, A.S., Williamson, W.R., Epstein, D., Wang, D., Rina, S., Meinertzhagen, I.A. and Hiesinger, P.R. (2012). The synaptic vesicle SNARE neuronal Synaptobrevin promotes endolysosomal degradation and prevents neurodegeneration in Drosophila. J. Cell. Biol., 196, 261-276.

  • Chan, C.C., Scoggin, S., Wang, D., Cherry, S., Dembo, T., Greenberg, B., Jin, E.J., Kuey, C., Lopez, A., Mehta, S.Q., Perkins, T.J., Brankatschk, M., Rothenfluh, A., Buszczak, M.*, and Hiesinger, P.R.* (2011). Systematic Discovery of Rab GTPases with Synaptic Functions in Drosophila. Current Biology, 21(20):1704-15.