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Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00470

Crowd control: effects of physical crowding on cargo movement in healthy and diseased neurons

  • 1Tata Institute of Fundamental Research, India

High concentration of cytoskeletal filaments, organelles, and proteins along with the space constraints due to the axon’s narrow geometry lead inevitably to intracellular physical crowding along the axon of a neuron. Local cargo movement is essential for maintaining steady cargo transport in the axon, and this may be impeded by physical crowding. Molecular motors that mediate active transport share movement mechanisms that allow them to bypass physical crowding present on microtubule tracks. Many neurodegenerative diseases irrespective of how they are initiated, show increased physical crowding owing to the greater number of stalled organelles and structural changes associated with the cytoskeleton. Increased physical crowding may be a significant factor in slowing cargo transport to synapses, contributing to disease progression and culminating in the dying back of the neuronal process. This review explores the idea that physical crowding can impede cargo movement along the neuronal process. We examine the sources of physical crowding and strategies used by molecular motors that might enable cargo to circumvent physically crowded locations. Finally, we describe sub-cellular changes in neurodegenerative diseases that may alter physical crowding and discuss the implications of such changes on cargo movement.

Keywords: Physical crowding, Axonal Transport, Neuron, neurodegeneration, Cytoskeleton, Organelles, molecular motors

Received: 16 Jun 2019; Accepted: 02 Oct 2019.

Copyright: © 2019 Sabharwal and Koushika. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sandhya P. Koushika, Tata Institute of Fundamental Research, Mumbai, 400005, Maharashtra, India, spkoushika@tifr.res.in