The clutch hypothesis revisited: Ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone

Jay, Daniel G.

doi:10.1002/1097-4695(200008)44:2<114::aid-neu3>3.0.co;2-8

Cited by 97 publications

(76 citation statements)

References 102 publications

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“…Rather than tensegrity, our findings are consistent with the clutch hypothesis [54,55] shown in Figure 3. That is, the key difference between microtubule function in low and high tension states appears to be how cells control the balance between actin polymerization and depolymerization [56,57].…”

Section: Microtubule Function and Tension State Of Cell-matrix Interasupporting

confidence: 89%

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Fibroblast mechanics in 3D collagen matrices☆

Rhee

Grinnell²

2007

Advanced Drug Delivery Reviews

167

115

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Connective tissues provide mechanical support and frameworks for the other tissues of the body. Type 1 collagen is the major protein component of ordinary connective tissue, and fibroblasts are the cell type primarily responsible for its biosynthesis and remodeling. Research on fibroblasts interacting with collagen matrices explores all four quadrants of cell mechanics: pro-migratory vs. pro-contractile growth factor environments on one axis; high tension vs. low tension cell-matrix interactions on the other. The dendritic fibroblast -probably equivalent to the resting tissue fibroblast -can be observed only in the low tension quadrant and generally has not been appreciated from research on cells incubated with planar culture surfaces. Fibroblasts in the low tension quadrant require microtubules for formation of dendritic extensions, whereas fibroblasts in the high tension quadrant require microtubules for polarization but not for spreading. Ruffling of dendritic extensions rather than their overall protrusion or retraction provides the mechanism for remodeling of floating collagen matrices, and floating matrix remodeling likely reflects a model of tissue mechanical homeostasis.

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Section: Microtubule Function and Tension State Of Cell-matrix Interasupporting

confidence: 89%

“…At a low tension state, microtubules act as an internal clutch for actin polymerization. Adapted from [54]. See [51] for additional details.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast mechanics in 3D collagen matrices☆

Rhee

Grinnell²

2007

Advanced Drug Delivery Reviews

167

115

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“…In particular, linkage with the F-actin network is thought to be especially critical because of its ability to create tension required for movement (Mitchison and Kirschner, 1988;Jay, 2000;Suter and Forscher, 2000;Dent and Gertler, 2003). The three variables in the hypothesis, actin assembly, engagement-disengagement of the clutch, and retrograde flow of F-actin, are "summed" to produce a net effect on the growth cone ranging from rapid extension to rapid retraction, with stationary states in between.…”

Section: Discussionmentioning

confidence: 99%

Studies on the Development and Behavior of the Dystrophic Growth Cone, the Hallmark of Regeneration Failure, in anIn VitroModel of the Glial Scar and after Spinal Cord Injury

et al. 2004

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We have developed a novel in vitro model of the glial scar that mimics the gradient of proteoglycan found in vivo after spinal cord injury. In this model, regenerated axons from adult sensory neurons that extended deeply into the gradient developed bulbous, vacuolated endings that looked remarkably similar to dystrophic endings formed in vivo. We demonstrate that despite their highly abnormal appearance and stalled forward progress, dystrophic endings are extremely dynamic both in vitro and in vivo after spinal cord injury. Time-lapse movies demonstrated that dystrophic endings continually send out membrane veils and endocytose large membrane vesicles at the leading edge, which were then retrogradely transported to the rear of the "growth cone." This direction of movement is contrary to membrane dynamics that occur during normal neurite outgrowth. As further evidence of this motility, dystrophic endings endocytosed large amounts of dextran both in vitro and in vivo. We now have an in vitro model of the glial scar that may serve as a potent tool for developing and screening potential treatments to help promote regeneration past the lesion in vivo.

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“…The flow may be the result of forces of membrane tension counteracting actin polymerization at the edge of the cell (Raucher and Sheetz, 2000) and/or contractile forces of myosin motors (Lin et al, 1996). The balance between forward movement of the cell and backward movement of the actin network is believed to depend on a clutch-like substrate-adhesion mechanism (Smilenov et al, 1999;Jay, 2000). When the actin network is tightly coupled to the substrate (clutch fully engaged), actin polymerization effectively pushes the plasma membrane forward, and myosin-based contraction pulls the cell body in the direction of the leading edge.…”

Section: Introductionmentioning

confidence: 99%

Tracking Retrograde Flow in Keratocytes: News from the Front

Vallotton

Danuser

Bohnet

et al. 2005

MBoC

130

111

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Actin assembly at the leading edge of the cell is believed to drive protrusion, whereas membrane resistance and contractile forces result in retrograde flow of the assembled actin network away from the edge. Thus, cell motion and shape changes are expected to depend on the balance of actin assembly and retrograde flow. This idea, however, has been undermined by the reported absence of flow in one of the most spectacular models of cell locomotion, fish epidermal keratocytes. Here, we use enhanced phase contrast and fluorescent speckle microscopy and particle tracking to analyze the motion of the actin network in keratocyte lamellipodia. We have detected retrograde flow throughout the lamellipodium at velocities of 1-3 m/min and analyzed its organization and relation to the cell motion during both unobstructed, persistent migration and events of cell collision. Freely moving cells exhibited a graded flow velocity increasing toward the sides of the lamellipodium. In colliding cells, the velocity decreased markedly at the site of collision, with striking alteration of flow in other lamellipodium regions. Our findings support the universality of the flow phenomenon and indicate that the maintenance of keratocyte shape during locomotion depends on the regulation of both retrograde flow and actin polymerization. INTRODUCTIONThe lamellipodium of motile cells is formed of a dense network of branched actin filaments (F-actin) polymerizing in the direction of cell movement. Network assembly at the leading edge is thought to generate the forces that push the plasma membrane forward (Theriot and Mitchison, 1991;Mogilner and Oster, 1996;Carlier et al., 2003;Pollard and Borisy, 2003). In most motile cells, the network is simultaneously transported away from the leading edge in a process known as retrograde flow (Cramer, 1997). The flow may be the result of forces of membrane tension counteracting actin polymerization at the edge of the cell (Raucher and Sheetz, 2000) and/or contractile forces of myosin motors (Lin et al., 1996). The balance between forward movement of the cell and backward movement of the actin network is believed to depend on a clutch-like substrate-adhesion mechanism (Smilenov et al., 1999;Jay, 2000). When the actin network is tightly coupled to the substrate (clutch fully engaged), actin polymerization effectively pushes the plasma membrane forward, and myosin-based contraction pulls the cell body in the direction of the leading edge. Conversely, when the clutch is loose, polymerization against the membrane pushes the network backward in concert with contraction pulling the actin network away from the leading edge. Thus, a possible mechanism for the cell to control its shape and net movement is by shifting the balance between protrusion and retrograde flow, supplementing the more widespread notion of spatial variation of actin assembly being the key regulator of cell motility (Pollard et al., 2000). Indeed, several studies report a relationship between retrograde flow and cell motion: the rate of retrograde...

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The clutch hypothesis revisited: Ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone

Cited by 97 publications

References 102 publications

Fibroblast mechanics in 3D collagen matrices☆

Fibroblast mechanics in 3D collagen matrices☆

Studies on the Development and Behavior of the Dystrophic Growth Cone, the Hallmark of Regeneration Failure, in anIn VitroModel of the Glial Scar and after Spinal Cord Injury

Tracking Retrograde Flow in Keratocytes: News from the Front

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