We are interested in the molecular mechanisms of intracellular vesicle traffic, in particular its intimate relationship with nervous system function, which we study in genetically manipulated fruit flies (Drosophila melanogaster).
Axonal transport and Rab proteins
Intracellular transport of organelles and molecules is vital for all cells, and particularly important for neurons due to their extreme polarity and size. Cargoes transported inside neurons include synaptic vesicle precursors, dense core vesicles, endosomes, lysosomes, autophagosomes, neurotransmitter receptors, ion channels, mRNA, neurofilaments, and scaffolding proteins. Deficient intracellular transport in neurons is a very common finding in neurological disease.
The evolutionary highly conserved family of small GTPases denoted Rab proteins (Rabs) are master regulators of intracellular transport. They control budding of transport vesicles from the donor compartment, binding of the vesicles to molecular motors (kinesin, dynein, myosin), and vesicle tethering and fusion to the target compartment.
Currently, we pursue the molecular principles underlying axonal transport of dense core vesicles, which contain neuropeptides, peptide hormones, and neurotrophic factors. Recently, we have found that Rab2 is required for axonal transport of both dense core vesicles and endo-lysosomal organelles (Lund et al., Cell Reports 2021). We have previously demonstrated an important role for Rab2 also in the biogenesis of lysosomes (Lund et al., Autophagy 2018).