Bidirectional actin transport is influenced by microtubule and actin stability

Local and long-distance transport of cytoskeletal proteins is vital to neuronal maintenance and growth. Though recent progress has provided insight into the movement of microtubules and neurofilaments, mechanisms underlying the movement of actin remain elusive, in large part due to rapid transitions...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2015-11, Vol.72 (21), p.4205-4220
Main Authors: Chetta, Joshua, Love, James M., Bober, Brian G., Shah, Sameer B.
Format: Article
Language:English
Subjects:
Actins - genetics
Actins - metabolism
Animals
Axonal Transport - physiology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cells, Cultured
Cellular biology
Cytoskeleton
Cytoskeleton - metabolism
Depsipeptides - pharmacology
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
Life Sciences
Microtubules - drug effects
Microtubules - metabolism
Mitochondria - metabolism
Models, Theoretical
Neurons - cytology
Neurons - metabolism
Nocodazole - pharmacology
Protein Transport
Pseudopodia - metabolism
Rats
Regression Analysis
Research Article
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Summary:Local and long-distance transport of cytoskeletal proteins is vital to neuronal maintenance and growth. Though recent progress has provided insight into the movement of microtubules and neurofilaments, mechanisms underlying the movement of actin remain elusive, in large part due to rapid transitions between its filament states and its diverse cellular localization and function. In this work, we integrated live imaging of rat sensory neurons, image processing, multiple regression analysis, and mathematical modeling to perform the first quantitative, high-resolution investigation of GFP-actin identity and movement in individual axons. Our data revealed that filamentous actin densities arise along the length of the axon and move short but significant distances bidirectionally, with a net anterograde bias. We directly tested the role of actin and microtubules in this movement. We also confirmed a role for actin densities in extension of axonal filopodia, and demonstrated intermittent correlation of actin and mitochondrial movement. Our results support a novel mechanism underlying slow component axonal transport, in which the stability of both microtubule and actin cytoskeletal components influence the mobility of filamentous actin.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-015-1933-z