Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin

Ganguly, Archan; Han, Xuemei; Das, Utpal; Wang, Lina; Loi, Jonathan; Sun, Jichao; Gitler, Daniel; Caillol, Ghislaine; Leterrier, Christophe; Yates, John R.; Roy, Subhojit

doi:10.1083/jcb.201604028

Cited by 25 publications

(22 citation statements)

References 68 publications

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“…What are the mechanisms underlying this transport? Using livecell imaging and fluorescent probes, more recent studies suggest that dynein motors are involved in both anterograde and retrograde transport of micro tubules 107,108 , whereas superresolution microscopy has started to unravel the elusive structure of slowtransport cargoes 109 . Microtubule movement in other cell types is well established, providing a precedent 110,111 .…”

Section: Box 3 | Stereotypical Development Of Neurons In Culturementioning

confidence: 99%

The nano-architecture of the axonal cytoskeleton

2017

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The corporeal beauty of the neuronal cytoskeleton has captured the imagination of generations of scientists. One of the easiest cellular structures to visualize by light microscopy, its existence has been known for well over 100 years, yet we have only recently begun to fully appreciate its intricacy and diversity. Recent studies combining new probes with super-resolution microscopy and live imaging have revealed surprising details about the axonal cytoskeleton and, in particular, have discovered previously unknown actin-based structures. Along with traditional electron microscopy, these newer techniques offer a nanoscale view of the axonal cytoskeleton, which is important for our understanding of neuronal form and function, and lay the foundation for future studies. In this Review, we summarize existing concepts in the field and highlight contemporary discoveries that have fundamentally altered our perception of the axonal cytoskeleton.

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Section: Box 3 | Stereotypical Development Of Neurons In Culturementioning

confidence: 99%

The nano-architecture of the axonal cytoskeleton

2017

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“…For example, several chaperones, including Hsp27 (38), Hsc70 (39), Hsp70 (40,41), Hsp90 (42), Hsp110 (43), and FKBP12 and Pin1 family members (44), have all been implicated in tau triage, many of which physically associate with tau via the MTBR domain (39), which harbors most of the acetylated lysine residues. Hsc70 in particular may be critical for packaging and transporting tau complexes via slow axonal transport (45,46). Furthermore, chaperone inhibition has been linked to neuroprotection against tau-mediated toxicity (47)(48)(49)(50).…”

Section: A Tau K280q Mutation Suppresses P301s Pathologymentioning

confidence: 99%

A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation

Ajit

Trzeciakiewicz

Tseng

et al. 2019

Journal of Biological Chemistry

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“…Although radiolabeling studies defined the various classes of axonal transport, the movement cannot be visualized by these methods. More recently, we developed a quantitative imaging assay to visualize slow axonal transport in cultured neurons (Ganguly et al, 2017;Scott et al, 2011;Tang et al 2013). In these experiments, proteins known to move in slow axonal transport (as shown by radiolabeling techniques) are tagged to photoactivatable GFP (PAGFP) and transfected in cultured neurons.…”

Section: Biased Anterograde Flow Of Axonal Actinmentioning

confidence: 99%

Processive movement of Actin by Biased Polymerization: A new paradigm of Axonal Transport

Chakrabarty

Dubey

Tang

et al. 2017

Preprint

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Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/dis-assembly events (“hotspots”) and elongating polymers along the axon-shaft (“trails”). Using a combination of live imaging, super-resolution microscopy, and modeling, here we explore how these axonal actin dynamics can lead to processive transport. We found abundant actin nucleation, along with a slow, anterogradely-biased flow of actin in axon-shafts. Starting with first principles of monomer/filament assembly – and incorporating imaging data – we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to an anterogradely-biased flow of the population, at rates consistent with slow transport. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin. This mechanism is distinct from polymer-sliding, and seems well suited to convey highly dynamic cytoskeletal cargoes.AcknowledgementsThis work was supported by an NIH grant to SR (R01NS075233). The authors thank Stephanie Gupton (UNC) for the Mena/Vasp constructs.

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Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin

Abstract: Using proteomics, live microscopy, and superresolution microscopy, Ganguly et al. offer insight into the molecular composition of cytosolic cargo complexes conveyed in slow axonal transport, identifying the heat shock protein Hsc70 as a major regulator of this transport.

Cited by 25 publications

References 68 publications

The nano-architecture of the axonal cytoskeleton

The nano-architecture of the axonal cytoskeleton

A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation

Processive movement of Actin by Biased Polymerization: A new paradigm of Axonal Transport

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