MAR 14, 2018 12:00 PM PDT

Decoding How Clathrin is Transported to Distal Synapses Along Axons

Presented at: Neuroscience 2018
C.E. Credits: P.A.C.E. CE Florida CE
Speakers
  • Postdoctoral Scholar, University of California, San Diego
    Biography
      Archan Ganguly received his graduate training as an electrophysiologist at Ohio University. His graduate work revealed the role of cAMP signaling on modulating inhibitory synaptic plasticity in Drosophila neurons and shows how inhibition is altered in learning and memory mutants. After completing graduate school, Archan started working as a post-doctoral fellow in Dr. Subhojit Roy's lab at University of California San Diego. In the Roy lab, he unraveled the mechanisms by which several proteins required to facilitate synaptic plasticity are transported to distal pre-synaptic botuons along axons. After a highly productive stint in the Roy lab, Archan is now a post-doctoral fellow in the laboratory of Prof. Susan Ackerman at University of California San Diego. In the Ackerman lab, he is utilizing his training as an electrophysiologist to examine changes in synaptic transmission in mouse models of neurodegeneration.

    Abstract:

    Clathrin mediated endocytosis (CME) at pre-synaptic terminals is functionally coupled to neuro-transmitter release. Like other cytosolic proteins, clathrin is synthesized in cell-bodies and conveyed into axons and synapses via slow axonal transport. Although the ‘triskelial’ structural conformation and endocytic function of clathrin at synapses is well-established, the cargo-structure or transport behavior of clathrin molecules moving in slow axonal transport is virtually unknown. We defined the cargo-composition and transport-kinetics of clathrin assemblies in axons using a combination of live-cell imaging, mass-spectrometry and correlative electron microscopy in primary hippocampal cultures and neurons in-vivo. We found that axonal clathrin is transported as a unique, stable cargo-complex that is distinct from the known ephemeral triskelial structures that exist at synapses and dendrites. While its transport-kinetics resembles other slow-component cargoes, surprisingly, the transport-complex contains both clathrin assembly and disassembly proteins and is ultra structurally distinct from any known clathrin assemblage. Further, we demonstrate that the stable transported clathrin cargo complex is deposited at en passant boutons along axons. Our studies thus uncover a previously-unknown form of clathrin and clarify mechanistic details of its slow transport into axons.


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