[Seminar] Neuronal Wiring Mechanisms: Balancing Acts of Small GTPases Control Neuronal Morphogenesis and Function by Dr.Tracy S. Tran ( Rutgers University )

A seminar by Tracy S. Tran, PhD, Professor in Neurobiology, Rutgers University, NJ, will be hosted by Prof. Yoshida.

[ Keywords ] Dendrite elaboration, Cortical Neurons, Cerebellar granule cells, Purkinje neurons, Proliferation

Abstract

How neuronal connections are assembled and disassembled leading to functional neural circuits, and how these connections are refined and maintained in health and disease are fundamental and unresolved questions in neuroscience. The determinants for the precise and diverse neuronal connections are largely regulated by extracellular guidance cues and their specific receptors on neurons, when engaged must properly balance the activation and/or inhibition of complex intracellular signaling cascades to induce diverse neuronal morphogenesis (of axons and dendrites). In a recent project, we used sophisticated mouse genetics, biochemical, molecular and cellular approaches in combination with behavioral assays to demonstrated distinct amino acid motifs (KRK and LVS) within the Plexin-A4 receptor cytoplasmic domain, are required to coordinate the downstream GTPases (Rac and Rho) to promote the guidance cue Sema3A mediated cortical neuron dendritic elaboration, which shed light on how the disparate functions of axon guidance and dendrite development are accomplished by the same ligand-receptor pair in vivo (doi:10.1126/scisignal.adh7673; 10.1523/JNEUROSCI.2730-19.2020). In the second half of the talk, we will focus on a new project involving members of the Rab GTPase family, Rab11, known to regulate recycling endosomes of the secretory pathway. We uncovered novel roles for Rab11 in balancing cerebellar granule cell and Purkinje neuron development. Finally, we investigated the distinct functions of the receptor, Neuropilin 2, in balancing excitatory and inhibitory circuit development and its role in neurological disorders such as autism spectrum disorder and childhood epilepsy, but due to time limit will not be discuss in today’s talk. Instead, our recent works could be found here, doi: 10.1038/s41380-024- 02839-4; 10.1038/s41398-021-01655-6; 10.1523/JNEUROSCI.1965-21.2022;10.1523/JNEUROSCI.1006-19.2019.