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Measuring Axonal Cargo Transport in Mouse Primary Cortical Cultured Neurons
Published on: February 24, 2023
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Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner
Anand N Rao1, Ankita Patil1, Mark M Black2
1Department of Neurobiology and Anatomy, Drexel University, Philadelphia, PA 19129, USA.
Cell Reports
|June 15, 2017
Summary
A motor-based mechanism involving cytoplasmic dynein sorts axonal microtubules, establishing a plus-end-out pattern. Inhibiting dynein disrupts transport and causes minus-end-out microtubules to accumulate.
Area of Science:
- Cell Biology
- Neuroscience
- Biophysics
Background:
- Axonal microtubules exhibit a predominant plus-end-out polarity.
- Understanding the mechanisms governing this organization is crucial for neuronal function.
Purpose of the Study:
- To investigate a motor-based mechanism for axonal microtubule polarity sorting.
- To determine the role of cytoplasmic dynein in this process.
Main Methods:
- Experimental inhibition of cytoplasmic dynein in axons.
- Computational modeling of microtubule transport dynamics.
- Assessment of microtubule polarity and transport following TRIM46 depletion.
Main Results:
- Acute inhibition of cytoplasmic dynein disrupted bi-directional microtubule transport.
- Minus-end-out microtubules accumulated in the axon upon dynein inhibition.
- Computational models indicated dynein, kinesin, and cross-linkers are necessary for polarity maintenance.
- TRIM46 depletion altered microtubule transport, consistent with model predictions.
Conclusions:
- Cytoplasmic dynein plays a critical role in axonal microtubule polarity sorting.
- A combination of motor proteins and cross-linking factors establishes and maintains the plus-end-out microtubule organization.
- This motor-based mechanism is essential for proper axonal microtubule organization.
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