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Journal article
Polarity sorting of axonal microtubules: a computational study
Molecular biology of the cell, v 28(23), pp 3271-3285
07 Nov 2017
PMID: 28978741
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We present a computational model to test a "polarity sorting" mechanism for microtubule (MT) organization in developing axons. We simulate the motor-based axonal transport of short MTs to test the hypothesis that immobilized cytoplasmic dynein motors transport short MTs with their plus ends leading, so "mal-oriented" MTs with minus-end-out are transported toward the cell body while "correctly" oriented MTs are transported in the anterograde direction away from the soma. We find that dynein-based transport of short MTs can explain the predominately plus-end-out polarity pattern of axonal MTs but that transient attachments of plus-end-directed motor proteins and nonmotile cross-linker proteins are needed to explain the frequent pauses and occasional reversals observed in live-cell imaging of MT transport. Static cross-linkers increase the likelihood of a stalled "tug-of-war" between retrograde and anterograde forces on the MT, providing an explanation for the frequent pauses of short MTs and the immobility of longer MTs. We predict that inhibition of the proposed static cross-linker will produce disordered transport of short MTs and increased mobility of longer MTs. We also predict that acute inhibition of cytoplasmic dynein will disrupt the polarity sorting of MTs by increasing the likelihood of "incorrect" sorting of MTs by plus-end-directed motors.
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Details
- Title
- Polarity sorting of axonal microtubules: a computational study
- Creators
- Erin M. Craig - Central Washington UniversityHoward T. Yeung - Central Washington UniversityAnand N. Rao - Drexel UniversityPeter W. Baas - Drexel University
- Publication Details
- Molecular biology of the cell, v 28(23), pp 3271-3285
- Publisher
- Amer Soc Cell Biology
- Number of pages
- 15
- Grant note
- F31NS093748 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 1F31NS093748-01A1 / National Research Service Award from the NINDS R01 NS28785 / National Institute of Neurological Disorders and Stroke (NINDS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000414552900014
- Scopus ID
- 2-s2.0-85033463355
- Other Identifier
- 991019167851604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology