Axonal transport

Investigators: Bianxiao Cui, PhD
Associate Professor of Chemistry, Stanford University

Investigator's profile

Professor Cui develops new physical and chemical approaches to study biological processes in neurons, with particular focus on long-range signal propagation in axons and its implications in neurodegenerative disease. Current work in the Cui Lab seeks to understand neuronal signal propagation, with three major research directions: 1) investigating axonal transport processes using optical imaging, magnetic and optical trapping, and a microfluidic platform; 2) developing vertical nanopillar-based electric and optic sensors for sensitive detection of biological functions; 3) using optogenetics to investigate temporal and spatial control of intracellular signaling pathways.

Significance & Background

Figure 1: Nanoparticle assisted optical tethering of endosomes in axons.

In neurons, the axon acts as a conduit for organized transport of materials between the cell body and the synapse. The extreme lengths and narrow calibers of axons, along with the large amount of materials that must be transported through axons represent unique challenges for neurons. Defective axonal transport, such as accumulation of axonal cargoes and slower transport rate, has been linked with a range of neurodegenerative diseases. To this end, dynein-dependent transport of organelles from the axon terminals to the cell bodies is essential to the survival and function of neurons. Hence, it is important to study molecular mechanism associated with retrograde axonal transport of neurotrophins and how this essential process is coordinated. However, quantitative knowledge of the transport process, especially of dyneins and axonal organelles and their collective function during this long-distance transport, is lacking because current technologies to measure these are not available for neurons.

Approach

Figure 2: Magneto-fluorescent particles. (a) Absorbance and fluorescence spectrum of non-blinking, uniform CdSeCdS core-shell QDs with unity QY and narrow emission linewidths [2]. (b) Magnetofluorescent core-shell superparticles compromised of a Fe3O4 core and a CdSeCdS shell (Scale bar 15 nm) [3].
The Cui lab has developed a new method termed nanoparticle-assisted optical tethering of endosomes (NOTE) that made it possible to study the cooperative mechanics of dyneins on retrograde axonal endosomes in live neurons [1] (Fig. 1). The method uses magneto fluorescent particels recently developed by LBRC [3] (Fig. 2). In this method, the opposing force from an elastic tether causes the endosomes to gradually stall under load and detach with a recoil velocity proportional to the dynein forces. These recoil velocities reveal that the axonal endosomes, despite their small size, can recruit up to 7 dyneins that function as independent mechanical units stochastically sharing load, which is vital for robust retrograde axonal transport. The Cui group has shown that NOTE, which relies on controlled generation of reactive oxygen species, is a viable method to manipulate small cellular cargos that are beyond the reach of current technology. The Cui lab will further develop techniques beyond NOTE to study axonal transport.

Center offering

LBRC provides novel magneto-fluorescent nanoparticles enabling Cui lab to manipulate small cellular cargos to study mechanochemical transduction of dyneins on the single molecular level.

References

  1. "Nanoparticle-assisted optical tethering of endosomes reveals the cooperative function of dyneins in retrograde axonal transport," Scientific Reports, 5: 18059, Dec. 2015. [ Pubmed ]
  2. "Compact high-quality CdSe/CdS core/shell nanocrystals with narrow emission linewidths and suppressed blinking," Nature Materials, 12(5), pp. 445-451, May 2013. [ Pubmed ]
  3. "Magneto-Fluorescent Core-Shell Supernanoparticles," Nature Comm., 5: 5093, Oct. 2014. [ Pubmed ]