Endosome-associated Rab GTPases control distinct aspects of neuronal morphogenesis and circuit assembly

Neural circuits shape all brain functions and govern the ways in which we sense and interact with the world, so it is crucial that we understand the molecular mechanisms underlying their development. Precise neural circuit assembly is largely mediated by cell surface proteins (CSPs), which enable neurons to transduce extracellular cues into the intracellular signaling cascades that guide neurites to their proper positions in the developing brain. The amount and presence of CSPs at the plasma membrane can be regulated by endocytosis, which can result in their degradation in lysosomes, trafficking to a new location, or recycling back to the plasma membrane, all of which impact their signaling. However, the specific steps in the endocytic pathway that are important for circuit assembly are largely opaque. The Rab family of small GTPases plays important roles in compartmentalizing endocytic functions and coordinating the transport of endocytic cargos to membrane compartments such as early endosomes, recycling endosomes, late endosomes, and lysosomes. Focusing on distinct Rabs allowed for the characterization of the roles of distinct endocytic pathways in neuronal morphology and the assembly of the Drosophila olfactory circuit. In particular, we focused on Rab5, which localizes to early endosomes, Rab11, which localizes to recycling endosomes, and Rab7, which localizes to late endosomes. Through clonal analysis, loss of each of these Rabs resulted in distinct defects in wiring as well as dendrite and axon morphology in a cell-type specific manner. Additionally, the loss of Rab11 or Rab7 altered early endosome populations. These results emphasize that cells use specific endocytic pathways to regulate CSP trafficking and control neuronal morphogenesis and circuit assembly.