Rapid Movements of Vimentin on Microtubule Tracks: Kinesin-dependent Assembly of Intermediate Filament Networks

Prahlad, Veena; Yoon, Miri; Moir, Robert D.; Vale, Ronald D.; Goldman, Robert D.

doi:10.1083/jcb.143.1.159

Cited by 320 publications

(342 citation statements)

References 60 publications

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“…Vimentin and other Type III IF proteins such as peripherin exist in several structural forms including non-filamentous particles, short filaments (or squiggles) and long filaments [18,19]. During the early stages of fibroblast and nerve cell spreading, much of the IF protein is in the form of particles that are subsequently converted into short filaments.…”

Section: Recent Insights Into Intermediate Filament Structure and Assmentioning

confidence: 99%

“…During the early stages of fibroblast and nerve cell spreading, much of the IF protein is in the form of particles that are subsequently converted into short filaments. The short filaments, in turn, appear to link in tandem to form longer IF [18]. While the exact state of IF protein in the particles is unknown, it is likely that they contain high concentrations of filament precursors such as ULFs.…”

Section: Recent Insights Into Intermediate Filament Structure and Assmentioning

confidence: 99%

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Intermediate filaments: versatile building blocks of cell structure

Goldman

Grin

Mendez

et al. 2008

Current Opinion in Cell Biology

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SummaryCytoskeletal intermediate filaments (IF) are organized into a dynamic nano-fibrillar complex that extends throughout mammalian cells. This organization is ideally suited to their roles as response elements in the subcellular transduction of mechanical perturbations initiated at cell surfaces. IF also provide a scaffold for other types of signal transduction which together with molecular motors ferries signaling molecules from the cell periphery to the nucleus. Recent insights into their assembly highlight the importance of co-translation of their precursors, the hierarchical organization of their subunits in the formation of unit length filaments (ULF), and the linkage of ULF into mature apolar IF. Analyses by atomic force microscopy reveal that mature IF are flexible and can be stretched to over 300% of their length without breaking, suggesting that intrafilament subunits can slide past one another when exposed to mechanical stress and strain. IF also play a role in the organization of organelles by modulating their motility and providing anchorage sites within the cytoplasm.

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Section: Recent Insights Into Intermediate Filament Structure and Assmentioning

confidence: 99%

Section: Recent Insights Into Intermediate Filament Structure and Assmentioning

confidence: 99%

Intermediate filaments: versatile building blocks of cell structure

Goldman

Grin

Mendez

et al. 2008

Current Opinion in Cell Biology

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“…Unlike the homogenous staining characteristics of WT astrocytes, Vim KO astrocytes revealed two phenotypes of GFAP staining cells. A majority (ϳ85-90%) of cells contained filamentous GFAP and the remaining cells expressed GFAP as short filament squiggles (26). The control cells showing both phenotypes is presented in Fig.…”

Section: Wfa Targets Vimentin and Gfap Expression In Astrocytes-mentioning

confidence: 99%

Withaferin A Targets Intermediate Filaments Glial Fibrillary Acidic Protein and Vimentin in a Model of Retinal Gliosis

Bargagna‐Mohan

Paranthan

Hamza

et al. 2010

Journal of Biological Chemistry

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Gliosis is a biological process that occurs during injury repair in the central nervous system and is characterized by the overexpression of the intermediate filaments (IFs) glial fibrillary acidic protein (GFAP) and vimentin. A common thread in manyThe overexpression of glial fibrillary acidic protein (GFAP) 2 with vimentin is a hallmark of reactive gliosis in the central nervous system (CNS) (1, 2). These intermediate filaments (IFs) are expressed by reactive astrocytes and macro-and microglia during traumatic and inflammatory injury and in a range of CNS degenerative diseases (2). In fact, an enigma of major retinal diseases, including age-related macular degeneration, glaucoma, diabetic retinopathy, and retinopathy of prematurity, is retinal gliosis, for which there is no available clinical treatment (3-5).Important fundamental insights on the structural and mechanical functions of IFs (6, 7) have now been validated in mouse lines deficient in type III IFs (2). These studies have illuminated that, whereas overexpression of vimentin and GFAP during CNS stress response and injury repair contributes to scar formation (8), their deficiency can be protective of tissue functions in certain contexts. For instance, pathogenic angiogenesis is impaired in vimentin-deficient (Vim KO) mice due to the decreased ability of newly formed blood vessels to cross the retinal inner limiting membrane in the model of hypoxia-induced retinal neovascularization (9). Interestingly, that study also identified in vimentin and GFAP double deficient (Vim GFAP dKO) mice, and to a lesser extent in Vim KO mice, that the retinal ganglion layer is highly sensitive to mechanical stress, which was not observed in GFAP KO mice. Pathological neovascularization was also reduced in Vim KO mice in the corneal alkali injury model (10) and delayed vascularization in skin injury model (11), which is attributed to defective vascular endothelial cell integrity (12), because vimentin is the sole type III IF expressed in endothelial cells (13). On the other hand, Vim GFAP dKO mice subjected to spinal cord or brain injury recover favorably with improvement of glial scars (14). In fact, the complete absence of type III IFs in Vim GFAP dKO mice helps promote axonal regeneration and regain ambulatory function after spinal cord injury (15). These Vim GFAP dKO

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“…Conventional kinesin is a molecular motor that is thought to transport membrane organelles (1) and intermediate filaments (2,3) along microtubules. In higher eukaryotes, conventional kinesin is composed of two heavy chains (∼120 kDa) and two light chains (60-80 kDa) (4).…”

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confidence: 99%

ATPase Kinetic Characterization and Single Molecule Behavior of Mutant Human Kinesin Motors Defective in Microtubule-Based Motility

et al. 2000

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Conventional kinesin is a microtubule-based motor protein that is an important model system for understanding mechanochemical transduction. To identify regions of the kinesin protein that participate in microtubule binding and force production, Woehlke et al. [(1997) Cell 90, 207-216] generated 35 alanine mutations in solvent-exposed residues. Here, we have performed presteady-state kinetic and single molecule motility analyses on three of these mutants [Y138A, loop 11 triple (L248A/D249A/E250A), and E311A] that exhibited a similar ∼3-fold reduction in both microtubule gliding velocity and microtubulestimulated ATPase activity. All mutants showed normal second-order ATP binding kinetics, indicating correct folding of the active site. The Y138A and loop 11 triple mutants were defective both in nucleotide hydrolysis and in microtubule-stimulated ADP release rates, the latter suggesting a defect in allosteric communication between the microtubule and the active site. A single molecule fluorescence assay further revealed that the loop 11 mutant is defective in initiating processive motion, suggesting that this loop is important for the initial contact between kinesin and the microtubule. Y138A, on the other hand, can bind to the microtubule normally but cannot move processively. For E311A, neither the rate of nucleotide hydrolysis nor ADP release could account for its slower ATPase and gliding velocity, which suggests that either phosphate release or a conformational transition is rate-limiting in this mutant. The single molecule assay showed that E311A has a reduced velocity of movement, but is not defective in processivity. Thus, while these mutants behave similarly in solution ATPase and multiple motor gliding assays, kinetic and single molecule analyses reveal defects in distinct processes in kinesin's mechanochemical cycle.

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Rapid Movements of Vimentin on Microtubule Tracks: Kinesin-dependent Assembly of Intermediate Filament Networks

Cited by 320 publications

References 60 publications

Intermediate filaments: versatile building blocks of cell structure

Intermediate filaments: versatile building blocks of cell structure

Withaferin A Targets Intermediate Filaments Glial Fibrillary Acidic Protein and Vimentin in a Model of Retinal Gliosis

ATPase Kinetic Characterization and Single Molecule Behavior of Mutant Human Kinesin Motors Defective in Microtubule-Based Motility

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