The Roles of Microtubules and Membrane Tension in Axonal Beading, Retraction, and Atrophy.

Abstract:

:Axonal beading, or the formation of a series of swellings along the axon, and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here, we report controlled experiments that can induce either beading or retraction and follow the time evolution of these responses. By making quantitative analysis of the shape modes under different conditions, measurement of membrane tension, and using theoretical considerations, we argue that membrane tension is the main driving force that pushes cytosol out of the axon when microtubules are degraded, causing axonal thinning. Under pharmacological perturbation, atrophy is always retrograde, and this is set by a gradient in the microtubule stability. The nature of microtubule depolymerization dictates the type of shape transformation, vis-à-vis beading or retraction. Elucidating the mechanisms of these shape transformations may facilitate development of strategies to prevent or arrest axonal atrophy due to neurodegenerative conditions.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Datar A,Ameeramja J,Bhat A,Srivastava R,Mishra A,Bernal R,Prost J,Callan-Jones A,Pullarkat PA

doi

10.1016/j.bpj.2019.07.046

subject

Has Abstract

pub_date

2019-09-03 00:00:00

pages

880-891

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(19)30662-9

journal_volume

117

pub_type

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