Rapid movement of axonal neurofilaments interrupted by prolonged pauses

Wang, Lei; Ho, Chung Liang; Sun, Dongming; Liem, Ronald K.H.; Brown, Anthony

doi:10.1038/35004008

Cited by 308 publications

(427 citation statements)

References 34 publications

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“…With respect to motility, it has been demonstrated that peripherin and NF containing short filaments (or squiggles) move along MT tracks at rates up to 1-2 m/s in association with the molecular motors, kinesin, and cytoplasmic dynein (Yabe et al, 1999(Yabe et al, , 2000Prahlad et al, 2000;Shah et al, 2000;Wang et al, 2000;Helfand et al, 2002Helfand et al, , 2003. From these observations, it seems that the mechanisms governing the intracellular transport of short NF and peripherin squiggles are not fundamentally different from each other.…”

Section: Discussionmentioning

confidence: 79%

A Role for Intermediate Filaments in Determining and Maintaining the Shape of Nerve Cells

Helfand

Mendez

Pugh

et al. 2003

MBoC

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To date, the functions of most neural intermediate filament (IF) proteins have remained elusive. Peripherin is a type III intermediate filament (IF)protein that is expressed in developing and in differentiated neurons of the peripheral and enteric nervous systems. It is also the major IF protein expressed in PC12 cells, a widely used model for studies of peripheral neurons. Dramatic increases in peripherin expression have been shown to coincide with the initiation and outgrowth of axons during development and regeneration, suggesting that peripherin plays an important role in axon formation. Recently, small interfering RNAs (siRNA) have provided efficient ways to deplete specific proteins within mammalian cells. In this study, it has been found that peripherin-siRNA depletes peripherin and inhibits the initiation, extension, and maintenance of neurites in PC12 cells. Furthermore, the results of these experiments demonstrate that peripherin IF are critical determinants of the overall shape and architecture of neurons. INTRODUCTIONThe cytoskeleton of vertebrate cells consists of three major types of protein networks: intermediate filaments (IF), microfilaments (MF), and microtubules (MT). Intermediate filaments are the most diverse of the three because they are encoded by Ͼ65 genes, making the IF superfamily one of the 100 largest in the human genome (Hesse et al., 2001). These genes are developmentally regulated, resulting in the cell type-specific expression of IF. This is clearly evident in the nervous system, where at least seven different IF proteins are expressed, ranging from the complex neurofilament (NF) heteropolymers composed of the type IV triplet proteins NF-L, NF-M, and NF-H, to the simpler homopolymers of the type III IF protein peripherin (Leung et al., 1998). Peripherin forms the major IF system of peripheral and enteric neurons, and it is abundantly expressed in PC12 cells, a widely used model for studies of peripheral neurons (Parysek and Goldman, 1987;Leonard et al., 1988; Portier et al., 1983a,b).One of the hallmarks of mature or terminally differentiated neurons is their remarkable shape, highlighted by extremely long cytoplasmic processes such as axons. The initiation, extension, and maintenance of axons involve the coordinated interactions of different cytoskeletal proteins (Mueller, 1999;Dickson, 2002). To date, only MT and MF have been considered essential for growth cone activity and axon outgrowth (Letourneau, 1996). In contrast, the contribution of neural IF to these processes has not been defined.The expression patterns of neural IF are highly correlated with different phases of axonal development. Type III IF, such as peripherin and vimentin, are present throughout early stages of outgrowth, and later type IV NF triplet proteins are expressed as axons reach maturity (Cochard and Paulin, 1984;Troy et al., 1990a). In mature neurons, NF appear to be major determinants of axon caliber, and thus conduction velocity (Lasek et al., 1983;Hoffman et al., 1987). However, little is known about ...

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Section: Discussionmentioning

confidence: 79%

A Role for Intermediate Filaments in Determining and Maintaining the Shape of Nerve Cells

Helfand

Mendez

Pugh

et al. 2003

MBoC

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“…As transport function B, the Rice distribution was used (Eq. [6] and Fig. 3a), which has very few components close to zero even for the minimum average velocity and resembles a Gaussian distribution for higher average velocity.…”

Section: Transport Functionsmentioning

confidence: 86%

“…[5][6][7]) were fitted to the ON data SI c (x,t) by optimizing the model parameters in order to minimize the L 1 and L 2 norm. Generally, the L p norm is given by:…”

Section: Model Fittingmentioning

confidence: 99%

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Manganese transport in the rat optic nerve evaluated with spatial‐ and time‐resolved magnetic resonance imaging

Olsen

Kristoffersen

Thuen

et al. 2010

Magnetic Resonance Imaging

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Purpose: 1) To evaluate a novel theoretical model for in vivo axonal Mn 2þ transport with MRI data from the rat optic nerve (ON); and 2) to compare predictions from the new model with previously reported experimental data. Materials and Methods:Time-resolved in vivo T 1 -weighted magnetic resonance imaging (MRI) of adult female Sprague-Dawley rat (n ¼ 9) ON was obtained at different timepoints after intravitreal MnCl 2 injection. A concentration-dependent and a rate-dependent function for the Mn 2þ retinal ganglion cell (RGC) axon entrance was convolved with three different transport functions and each model system was optimized to fit the ON data.Results: The rate-limited input function gave a better fit to the data than the concentration-limited input. Simulations showed that the rate-limited input leads to a semilogarithmic relationship between injected dose and Mn 2þ concentration in the ON, which is in agreement with previously reported in vivo experiments. A random walk transport model and an anterograde predominant slow model gave a similar fit to the data, both better than an anterograde predominant fast model. Conclusion:The results indicate that Mn 2þ input into RGC axons is limited by a maximum entrance rate into the axons. Also, a wide range of apparent Mn 2þ transport rates seems to be involved, different from synaptic vesicle transport rates, meaning that manganese does not depict synaptic vesicle transport rates directly.

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“…Studies in which fluorescent tags are placed on tubulin have allowed delineation of the microtubular organisation of the axon suggest that neurofilaments may move intermittently at fast speeds (up to 2 mm/s) interspersed with a period of no motion. 41 The overall result is of apparent slow axonal transport. A curious feature of this system is the wide variation in transport speeds for different molecules.…”

Section: Anterograde Transportmentioning

confidence: 99%

Circulation and axonal transport in the optic nerve

Morgan

2004

Eye

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Retinal ganglion cells are the output cells of the retina whose axons are under considerable metabolic stress in both health and disease states. They are highly polarised to ensure that mitochondria and enzymes involved in the generation of ATP are strategically concentrated to meet the local energy demands of the cell. In passing from the eye to the brain, axons are protected and supported by glial tissues and the blood supply of the optic nerve head is regulated to maintain the supply of oxygen and nutrients to the axons.In spite of this, the optic nerve head remains the point at which retinal ganglion cell axons are most vulnerable to the effects of increased intraocular pressure or ischaemia. Considerable work has been undertaken in this area to advance our understanding on the pathophysiology of axon damage and to develop new strategies for the prevention of retinal ganglion cell death.

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Rapid movement of axonal neurofilaments interrupted by prolonged pauses

Cited by 308 publications

References 34 publications

A Role for Intermediate Filaments in Determining and Maintaining the Shape of Nerve Cells

A Role for Intermediate Filaments in Determining and Maintaining the Shape of Nerve Cells

Manganese transport in the rat optic nerve evaluated with spatial‐ and time‐resolved magnetic resonance imaging

Circulation and axonal transport in the optic nerve

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