Faculty Opinions recommendation of Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth.

2013 ◽  
Author(s):  
Peng T Khaw ◽  
Hari Jayaram ◽  
Alastair Lockwood
Keyword(s):  
Growth Cone ◽  
Neurite Growth

scholarly journals Growth cone collapse and inhibition of neurite growth by Botulinum neurotoxin C1: a t-SNARE is involved in axonal growth.

1996 ◽  
Vol 134 (1) ◽  
pp. 205-215 ◽  
Author(s):  
M Igarashi ◽  
S Kozaki ◽  
S Terakawa ◽  
S Kawano ◽  
C Ide ◽  
...  
Keyword(s):  
Growth Cone ◽  
Axonal Growth ◽  
Normal Growth ◽  
Neurite Growth ◽  
Total Surface Area ◽  
Central Domain ◽  
Growth Cone Collapse ◽  
Gradual Disappearance ◽  
Microscopic Studies ◽  
Presynaptic Protein

The growth cone is responsible for axonal growth, where membrane expansion is most likely to occur. Several recent reports have suggested that presynaptic proteins are involved in this process; however, the molecular mechanism details are unclear. We suggest that by cleaving a presynaptic protein syntaxin, which is essential in targeting synaptic vesicles as a target SNAP receptor (t-SNARE), neurotoxin C1 of Clostridium botulinum causes growth cone collapse and inhibits axonal growth. Video-enhanced microscopic studies showed (a) that neurotoxin C1 selectively blocked the activity of the central domain (the vesicle-rich region) at the initial stage, but not the lamellipodia in the growth cone; and (b) that large vacuole formation occurred probably through the fusion of smaller vesicles from the central domain to the most distal segments of the neurite. The total surface area of the accumulated vacuoles could explain the membrane expansion of normal neurite growth. The gradual disappearance of the surface labeling by FITC-WGA on the normal growth cone, suggesting membrane addition, was inhibited by neurotoxin C1. The experiments using the peptides derived from syntaxin, essential for interaction with VAMP or alpha-SNAP, supported the results using neurotoxin C1. Our results demonstrate that syntaxin is involved in axonal growth and indicate that syntaxin may participate directly in the membrane expansion that occurs in the central domain of the growth cone, probably through association with VAMP and SNAPs, in a SNARE-like way.

scholarly journals Delayed Retraction of Filopodia in Gelsolin Null Mice

1997 ◽  
Vol 138 (6) ◽  
pp. 1279-1287 ◽  
Author(s):  
Mei Lu ◽  
Walter Witke ◽  
David J. Kwiatkowski ◽  
Kenneth S. Kosik
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Neurite Growth ◽  
Time Lapse ◽  
Growth Cones ◽  
Wild Type ◽  
Dynamic Studies ◽  
Shape Changes ◽  
Time Lapse Video ◽  
Cultured Hippocampal Neurons

Growth cones extend dynamic protrusions called filopodia and lamellipodia as exploratory probes that signal the direction of neurite growth. Gelsolin, as an actin filament-severing protein, may serve an important role in the rapid shape changes associated with growth cone structures. In wild-type (wt) hippocampal neurons, antibodies against gelsolin labeled the neurite shaft and growth cone. The behavior of filopodia in cultured hippocampal neurons from embryonic day 17 wt and gelsolin null (Gsn−) mice (Witke, W., A.H. Sharpe, J.H. Hartwig, T. Azuma, T.P. Stossel, and D.J. Kwiatkowski. 1995. Cell. 81:41–51.) was recorded with time-lapse video microscopy. The number of filopodia along the neurites was significantly greater in Gsn− mice and gave the neurites a studded appearance. Dynamic studies suggested that most of these filopodia were formed from the region of the growth cone and remained as protrusions from the newly consolidated shaft after the growth cone advanced. Histories of individual filopodia in Gsn− mice revealed elongation rates that did not differ from controls but an impaired retraction phase that probably accounted for the increased number of filopodia long the neutrite shaft. Gelsolin appears to function in the initiation of filopodial retraction and in its smooth progression.

scholarly journals Computational modeling of neurons: intensity-duration relationship of extracellular electrical stimulation for changes in intracellular calcium

2016 ◽  
Vol 115 (1) ◽  
pp. 602-616 ◽  
Author(s):  
Robert D. Adams ◽  
Rebecca K. Willits ◽  
Amy B. Harkins
Keyword(s):  
Electrical Stimulation ◽  
Intracellular Calcium ◽  
Growth Cone ◽  
Pulse Train ◽  
Neurite Growth ◽  
Growth Cones ◽  
Train Duration ◽  
Voltage Dependent ◽  
Duration Relationship ◽  
Relationship Of

In many instances of extensive nerve damage, the injured nerve never adequately heals, leaving lack of nerve function. Electrical stimulation (ES) has been shown to increase the rate and orient the direction of neurite growth, and is a promising therapy. However, the mechanism in which ES affects neuronal growth is not understood, making it difficult to compare existing ES protocols or to design and optimize new protocols. We hypothesize that ES acts by elevating intracellular calcium concentration ([Ca2+]i) via opening voltage-dependent Ca2+ channels (VDCCs). In this work, we have created a computer model to estimate the ES Ca2+ relationship. Using COMSOL Multiphysics, we modeled a small dorsal root ganglion (DRG) neuron that includes one Na+ channel, two K+ channels, and three VDCCs to estimate [Ca2+]i in the soma and growth cone. As expected, the results show that an ES that generates action potentials (APs) can efficiently raise the [Ca2+]i of neurons. More interestingly, our simulation results show that sub-AP ES can efficiently raise neuronal [Ca2+]i and that specific high-voltage ES can preferentially raise [Ca2+]i in the growth cone. The intensities and durations of ES on modeled growth cone calcium rise are consistent with directionality and orientation of growth cones experimentally shown by others. Finally, this model provides a basis to design experimental ES pulse parameters, including duration, intensity, pulse-train frequency, and pulse-train duration to efficiently raise [Ca2+]i in neuronal somas or growth cones.

Neurite growth cone-substratum adherance increases in vitro

1984 ◽  
Vol 12 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Ross W. Gundersen ◽  
John N. Barrett
Keyword(s):  
Growth Cone ◽  
Neurite Growth

scholarly journals Mitochondrial Dynamics Regulate Growth Cone Motility, Guidance, and Neurite Growth Rate in Perinatal Retinal Ganglion Cells In Vitro

2012 ◽  
Vol 53 (11) ◽  
pp. 7402 ◽  
Author(s):  
Michael B. Steketee ◽  
Stavros N. Moysidis ◽  
Jessica E. Weinstein ◽  
Alex Kreymerman ◽  
Jose P. Silva ◽  
...  
Keyword(s):  
Growth Rate ◽  
Retinal Ganglion Cells ◽  
Growth Cone ◽  
Ganglion Cells ◽  
Mitochondrial Dynamics ◽  
Neurite Growth ◽  
Retinal Ganglion

scholarly journals Differences in the organization of actin in the growth cones compared with the neurites of cultured neurons from chick embryos.

1983 ◽  
Vol 97 (4) ◽  
pp. 963-973 ◽  
Author(s):  
P C Letourneau
Keyword(s):  
Growth Cone ◽  
Actin Filaments ◽  
Electron Microscopic Observation ◽  
Neurite Growth ◽  
Growth Cones ◽  
Chick Embryos ◽  
Heavy Meromyosin ◽  
Electron Microscopic ◽  
Cytochemical Localization ◽  
Triton X

Sensory neurons from chick embryos were cultured on substrata that support neurite growth, and were fixed and prepared for both cytochemical localization of actin and electron microscopic observation of actin filaments in whole-mounted specimens. Samples of cells were treated with the detergent Triton X-100 before, during, or after fixation with glutaraldehyde to determine the organization of actin in simpler preparations of extracted cytoskeletons. Antibodies to actin and a fluorescent derivative of phallacidin bound strongly to the leading margins of growth cones, but in neurites the binding of these markers for actin was very weak. This was true in all cases of Triton X-100 treatment, even when cells were extracted for 4 min before fixation. In whole-mounted cytoskeletons there were bundles and networks of 6-7-nm filaments in leading edges of growth cones but very few 6-7-n filaments were present among the microtubules and neurofilaments in the cytoskeletons of neurites. These filaments, which are prominent in growth cones, were identified as actin because they were stabilized against detergent extraction by the presence of phallacidin or the heavy meromyosin and S1 fragments of myosin. In addition, heavy meromyosin and S1 decorated these filaments as expected for binding to F-actin. Microtubules extended into growth cone margins and terminated within the network of actin filaments and bundles. Interactions between microtubule ends and these actin filaments may account for the frequently observed alignment of microtubules with filopodia at the growth cone margins.

Steady growth cone currents revealed by a novel circularly vibrating probe: A possible mechanism underlying neurite growth

1985 ◽  
Vol 13 (1-2) ◽  
pp. 257-283 ◽  
Author(s):  
J.A. Freeman ◽  
P.B. Manis ◽  
G.J. Snipes ◽  
B.N. Mayes ◽  
P.C. Samson ◽  
...  
Keyword(s):  
Growth Cone ◽  
Neurite Growth ◽  
Vibrating Probe ◽  
Steady Growth

scholarly journals Vinaxanthone inhibits Semaphorin3A induced axonal growth cone collapse in embryonic neurons but fails to block its growth promoting effects on adult neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Evguenia Ivakhnitskaia ◽  
Matthew R. Chin ◽  
Dionicio Siegel ◽  
Victor H. Guaiquil
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Neuronal Cell ◽  
Neurite Growth ◽  
Cell Types ◽  
Pleiotropic Effect ◽  
In Vivo Models ◽  
Peripheral Neurons ◽  
Growth Cone Collapse

AbstractSemaphorin3A is considered a classical repellent molecule for developing neurons and a potent inhibitor of regeneration after nervous system trauma. Vinaxanthone and other Sema3A inhibitors are currently being tested as possible therapeutics to promote nervous system regeneration from injury. Our previous study on Sema3A demonstrated a switch in Sema3A’s function toward induction of nerve regeneration in adult murine corneas and in culture of adult peripheral neurons. The aim of the current study is to determine the direct effects of Vinaxanthone on the Sema3A induced adult neuronal growth. We first demonstrate that Vinaxanthone maintains its anti-Sema3A activity in embryonic dorsal root ganglia neurons by inhibiting Sema3A-induced growth cone collapse. However, at concentrations approximating its IC50 Vinaxanthone treatment does not significantly inhibit neurite formation of adult peripheral neurons induced by Sema3A treatment. Furthermore, Vinaxanthone has off target effects when used at concentrations above its IC50, and inhibits neurite growth of adult neurons treated with either Sema3A or NGF. Our results suggest that Vinaxanthone’s pro-regenerative effects seen in multiple in vivo models of neuronal injury in adult animals need further investigation due to the pleiotropic effect of Sema3A on various non-neuronal cell types and the possible effect of Vinaxanthone on other neuroregenerative signals.

scholarly journals UNC-45A is required for neurite extension via controlling NMII activation

2017 ◽  
Vol 28 (10) ◽  
pp. 1337-1346 ◽  
Author(s):  
Yoshie Iizuka ◽  
Ashley Mooneyham ◽  
Andrew Sieben ◽  
Kevin Chen ◽  
Makayla Maile ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Growth Cone ◽  
Molecular Mechanisms ◽  
Neurite Growth ◽  
Multiprotein Complex ◽  
Master Regulator ◽  
Neurite Extension ◽  
Cellular Processes ◽  
Neurite Elongation

UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins, which act as chaperones for conventional and nonconventional myosins. NMII mediates contractility and actin-based motility, which are fundamental for proper growth cone motility and neurite extension. The presence and role of UNC-45A in neuronal differentiation have been largely unknown. Here we demonstrate that UNC-45A is a novel growth cone–­localized, NMII-associated component of the multiprotein complex regulating growth cone dynamics. We show that UNC-45A is dispensable for neuron survival but required for neurite elongation. Mechanistically, loss of UNC-45A results in increased levels of NMII activation. Collectively our results provide novel insights into the molecular mechanisms of neurite growth and define UNC-45A as a novel and master regulator of NMII-mediated cellular processes in neurons.

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