Stop and Go: Proteins Important
in Alzheimer’s, Parkinson’s Disease Travel in the Slow
Researchers at the University
of Pennsylvania School of Medicine have been able to observe
proteins important in Alzheimer’s and Parkinson’s disease moving along axons, extensions of nerve cells that
carry proteins away from the cell body.
Axonal transport often breaks down and
many neurodegenerative diseases are characterized by defects
in this process.
The researchers devised a system to simultaneously
visualize the transport of two labeled slow proteins
in living cultured mouse axons. This clarified unique aspects
of slow-protein transport.
The study appeared in the Journal
Axonal transport often breaks down and many neurodegenerative
diseases are characterized by defects in this process. Of particular
interest is a group of transported proteins called slow component-b
that includes synuclein and tau, disease proteins involved in Parkinson’s
and Alzheimer’s disease, respectively, in addition to many
other proteins critical for axonal growth and regeneration.
Simultaneous video-microscopy of slow (red) and fast (green) transport proteins
Click on thumbnail
to view full-size image
“There are two basic transport groups called fast and slow
components, with a 200 to 300 fold difference in average velocities,” says
first author Subhojit Roy, MD, PhD, a neuropathologist and Research
Associate in the Department
of Pathology and Laboratory Medicine. “While
scientists have seen proteins in the fast component move rapidly
to the tip of the axon, until now, mechanisms of the slow movement
of these disease-related proteins have been unclear as their transport
had not been directly visualized.”
Slow transport protein alpha-synuclein moving
along an axon
Click on thumbnail
to view full-size image
Roy devised a system to simultaneously visualize the transport
of two labeled slow-component-b proteins in living cultured mouse
axons. This clarified unique aspects of slow-protein transport.
He found that the “slow” proteins actually showed rapid
bursts of movement followed by pauses. This intermittent transport
behavior of individual cargoes made the overall population slow
and suggests that fast and slow proteins use the same basic mechanisms
Surprisingly, the videos also revealed that multiple slow proteins
are transported together as “packets,” essentially
piggy-backing on each other, possibly on the same specialized proteins
motors. “It makes sense when you think about
it – why would the neurons spend so much energy transporting
proteins separately when they’re going to the same place
anyway, like car pooling” speculates Roy.
Simultaneous video-microscopy of slow (red) and fast (green) transport proteins: A
slow transport protein (alpha-synuclein) and a fast transport
protein (synaptophysin) was labeled red and green respectively
and both channels were obtained simultaneously using a
novel dual-cam system. For display, the red channel is
shifted vertically to allow visualization of both channels
independently. Images were taken at ~1 frame/0.6 seconds,
elapsed time in minutes:seconds is shown on the left. Note
that a single red (slow) particle moves towards the axon tip with pauses, while several green (fast) particles are rapidly transported in the same axon.
Video Credit: Subhojit Roy, MD, PhD, University
of Pennsylvania School of Medicine
QuickTime player may be required —
download a free copy here
“Our study reveals novel aspects of axonal transport of an
important class of proteins, namely the slow component-b proteins,
and also opens up new avenues for investigating axonal transport
defects in neurodegenerative diseases,” concludes Roy.
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