Tension- and Adhesion-Regulated Retraction of Injured Axons

Shao, Xueying; You, Ran; Hui, Tsz Hin; Fang, Chao; Gong, Zhiyuan; Yan, Zhenyu; Chang, Raymond Chuen‐Chung; Shenoy, Vivek B.; Lin, Yuan

doi:10.1016/j.bpj.2019.06.011

Cited by 16 publications

(20 citation statements)

References 62 publications

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“…Thus, the faster bond dissociation of these complexes, with or without mechanical forces, makes stimulation of retraction of neuronal processes unlikely. Therefore, Syndecan-4 appears to play a key role in modulating the speed of neuronal responses under pathological conditions ( Figure 5 ), in agreement with the rapid axon retraction observed in vivo ( Houle and Tessler, 2003 ) and in vitro ( Shao et al, 2019 ).…”

Section: Discussionsupporting

confidence: 81%

“…Here, we studied morphological neuronal changes stimulated by cell-cell communication between neurons and astrocytes through the cell adhesion molecules, Thy-1, α V β 3 integrin and Syndecan-4. It has also been reported that cell-extracellular matrix interactions play a key role in the regulation of neuronal process retraction ( Ahmad et al, 2000 ; Franze et al, 2009 ; Shao et al, 2019 ), as well as in the contraction of other cell types ( Okamoto et al, 1998 ). In our neurite retraction assays, CAD cells were seeded directly over standard tissue culture dishes without additional treatments (e.g., poly- L -lysine).…”

Section: Discussionmentioning

confidence: 99%

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Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Burgos‐Bravo

Martínez-Meza

Quest

et al. 2020

Front. Mol. Biosci.

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Inflammation contributes to the genesis and progression of chronic diseases, such as cancer and neurodegeneration. Upregulation of integrins in astrocytes during inflammation induces neurite retraction by binding to the neuronal protein Thy-1, also known as CD90. Additionally, Thy-1 alters astrocyte contractility and movement by binding to the mechano-sensors α V β 3 integrin and Syndecan-4. However, the contribution of Syndecan-4 to neurite shortening following Thy-1–α V β 3 integrin interaction remains unknown. To further characterize the contribution of Syndecan-4 in Thy-1-dependent neurite outgrowth inhibition and neurite retraction, cell-based assays under pro-inflammatory conditions were performed. In addition, using Optical Tweezers, we studied single-molecule binding properties between these proteins, and their mechanical responses. Syndecan-4 increased the lifetime of Thy-1–α V β 3 integrin binding by interacting directly with Thy-1 and forming a ternary complex (Thy-1–α V β 3 integrin + Syndecan-4). Under in vitro -generated pro-inflammatory conditions, Syndecan-4 accelerated the effect of integrin–engaged Thy-1 by forming this ternary complex, leading to faster neurite retraction and the inhibition of neurite outgrowth. Thus, Syndecan-4 controls neurite cytoskeleton contractility by modulating α V β 3 integrin mechano-receptor function. These results suggest that mechano-transduction, cell-matrix and cell-cell interactions are likely critical events in inflammation-related disease development.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Burgos‐Bravo

Martínez-Meza

Quest

et al. 2020

Front. Mol. Biosci.

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“…There thus appear to be at least two processes that account for the optimum-curve like distribution of regenerative capacity (see Fig. 5): First, the reduced capacity after injury very close to the soma might be due to an initial axonal retraction response (also known as axonal dieback) that has been suggested (after injury set with different methods) in other systems 47,48 . Second, additional processes must account for the decay of regenerative capacity farther away from the soma.…”

Section: Discussionmentioning

confidence: 99%

High-resolution mapping of injury-site dependent functional recovery in a single axon in zebrafish

Hecker

Anger

et al. 2020

Commun Biol

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In non-mammalian vertebrates, some neurons can regenerate after spinal cord injury. One of these, the giant Mauthner (M-) neuron shows a uniquely direct link to a robust survivalcritical escape behavior but appears to regenerate poorly. Here we use two-photon microscopy in parallel with behavioral assays in zebrafish to show that the M-axon can regenerate very rapidly and that the recovery of functionality lags by just days. However, we also find that the site of the injury is critical: While regeneration is poor both close and far from the soma, rapid regeneration and recovery of function occurs for injuries between 10% and 50% of total axon length. Our findings show that rapid regeneration and the recovery of function can be studied at remarkable temporal resolution after targeted injury of one single M-axon and that the decision between poor and rapid regeneration can be studied in this one axon.

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“…[ 28,29 ] Accordingly, subsequent reduction of these actomyosin tugging forces results in shrinkage and loss of FAs. [ 30,31 ] In contrast, other mechano‐adaptions can persist long past cessation of the original mechanical cue, resulting in lasting or even permanent changes in cell behavior; this is well illustrated by work from the Hinz and Anseth groups. The former showed that fibroblasts could be “activated” to a myofibroblast phenotype by culture on a stiff substrate, and that this transformation persisted through multiple population doublings, even after the cells were returned to a soft environment.…”

Section: Mechanotransduction and Mechanical Memorymentioning

confidence: 99%

“Looping In” Mechanics: Mechanobiologic Regulation of the Nucleus and the Epigenome

Dai

Heo

Mauck

2020

Adv Healthcare Materials

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cues, or "mechanical memory," results from the stable remodeling of various components of the cell. Defining of the mechanisms by which the cell forms and maintains mechanical memories will forward the development of new biomaterials with improved cell functionality. Importantly, converging strands of evidence have implicated the cell nucleus, the storehouse of the genome, as a critically important adaptive mechanosensor in all cells. [2,3] In particular, recent evidence has shown that forces can be directly transmitted to chromatin to alter gene expression. [4] In this review, we discuss the central importance of the cell nucleus and chromatin in understanding and manipulating mechanobiological pathways, and the manner in which extracellular mechanical cues are "looped in" (that is, transmitted to, interpreted by, and stored in) the epigenome and chromatin organization to direct cell fate. In Section 2, we define a framework for understanding how cells sense, transduce, and remember mechanical cues. In Section 3, we provide an overview of how the cell nucleus senses, transduces and adapts to mechanical forces. Following this, we describe in Section 4 how mechanical memories might be encoded within organized chromatin through molecular signaling as well as direct force-induced structural rearrangements. Finally, we conclude in Section 5, outlining new directions for the field in reducing this new knowledge to practice. Mechanotransduction and Mechanical MemoryIn this section, we review the concepts of mechanotransduction and mechanical memory in the mammalian cell. MechanotransductionThe last decade has witnessed a number of technological advances that enable the study of cell mechanics down to the sub-protein level, fostering a new understanding of the role of mechanobiological mechanisms in governing cell behavior (for a comprehensive overview of this topic, please refer to the following reviews [5,6] ). Indeed, it is now well accepted that mechanical cues play a fundamental role in directing cell behavior. Cells sense exogenous mechanical forces in addition to exerting their own. These processes are accomplished through the mechanobiological machinery of the cell-the force sensing (e.g., integrin based focal adhesions), [7] transmitting Cells respond to physical cues in their microenvironment. These cues result in changes in cell behavior, some of which are transient, and others of which are permanent. Understanding and leveraging permanent alteration of cell behavior induced by mechanical cues, or "mechanical memories," is an important aim in cell and tissue engineering. Herein, this paper reviews the existing literature outlining how cells may store memories of biophysical cues with a specific focus on the nucleus, the storehouse of information in eukaryotic cells. In particular, this review details mechanically driven adaptations in nuclear structure and genome organization and outlines potential mechanisms by which mechanical memories may be encoded within the structure and organization of the nucleus and ...

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Tension- and Adhesion-Regulated Retraction of Injured Axons

Cited by 16 publications

References 62 publications

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

Application of Force to a Syndecan-4 Containing Complex With Thy-1–αVβ3 Integrin Accelerates Neurite Retraction

High-resolution mapping of injury-site dependent functional recovery in a single axon in zebrafish

“Looping In” Mechanics: Mechanobiologic Regulation of the Nucleus and the Epigenome

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