Rho GTPases and axonal growth cone collapse

Plexins are widely expressed transmembrane proteins that mediate the effects of semaphorins. The molecular mechanisms of plexin-mediated signal transduction are still rather unclear. Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2–mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse.

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Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Journal of Visualized Experiments ◽

10.3791/58229 ◽

2018 ◽

Cited By ~ 1

Author(s):

Tomoharu Kuboyama

Keyword(s):

Growth Cone ◽

Axonal Growth ◽

Growth Cone Collapse ◽

Axonal Growth Cone

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hnRNP Q Regulates Internal Ribosome Entry Site-Mediated fmr1 Translation in Neurons

Molecular and Cellular Biology ◽

10.1128/mcb.00371-18 ◽

2018 ◽

Vol 39 (4) ◽

Cited By ~ 3

Author(s):

Jung-Hyun Choi ◽

Sung-Hoon Kim ◽

Young-Hun Jeong ◽

Sung Wook Kim ◽

Kyung-Tai Min ◽

...

Keyword(s):

Growth Cone ◽

Internal Ribosome Entry Site ◽

Rna Binding ◽

Regulatory Mechanism ◽

Fragile X ◽

Axonal Growth ◽

Entry Site ◽

Internal Ribosome Entry ◽

Growth Cone Collapse ◽

Axonal Growth Cone

ABSTRACT Fragile X syndrome (FXS) caused by loss of fragile X mental retardation protein (FMRP), is the most common cause of inherited intellectual disability. Numerous studies show that FMRP is an RNA binding protein that regulates translation of its binding targets and plays key roles in neuronal functions. However, the regulatory mechanism for FMRP expression is incompletely understood. Conflicting results regarding internal ribosome entry site (IRES)-mediated fmr1 translation have been reported. Here, we unambiguously demonstrate that the fmr1 gene, which encodes FMRP, exploits both IRES-mediated translation and canonical cap-dependent translation. Furthermore, we find that heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) acts as an IRES-transacting factor (ITAF) for IRES-mediated fmr1 translation in neurons. We also show that semaphorin 3A (Sema3A)-induced axonal growth cone collapse is due to upregulation of hnRNP Q and subsequent IRES-mediated expression of FMRP. These data elucidate the regulatory mechanism of FMRP expression and its role in axonal growth cone collapse.

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Oligodendrocytes repel axons and cause axonal growth cone collapse

Journal of Cell Science ◽

10.1242/jcs.92.1.93 ◽

1989 ◽

Vol 92 (1) ◽

pp. 93-100 ◽

Cited By ~ 1

Author(s):

J.W. Fawcett ◽

J. Rokos ◽

I. Bakst

Keyword(s):

Growth Cone ◽

Dorsal Root ◽

Axonal Growth ◽

Time Lapse ◽

Growth Cones ◽

Newborn Rats ◽

Growth Cone Collapse ◽

Axonal Growth Cone ◽

Video Studies ◽

Culture Surface

We have examined the interactions between axons regenerating from dorsal root ganglia (DRGs) derived from newborn rats and oligodendrocytes cultured by three different techniques. Cultures examined after 2 days have a profuse outgrowth of axons from the DRGs, forming a dense mat on the culture surface. However, the axons avoid growing on oligodendrocytes; axons are seen all around these cells, but do not grow over them. We have also performed time-lapse video studies of the interactions between axonal growth cones and oligodendrocytes. Axons grow normally until their growth cone comes into direct contact with an oligodendrocyte, following which the growth cone remains motile for 30–60 min, but without making any progress over the cell. The growth cone then suddenly collapses, and the axon retracts, leaving a thin strand in contact with the cell. After this a new growth cone is usually elaborated and the process repeated. Oligodendrocytes are therefore inhibitory to axonal growth, and this may partially explain the failure of axons to regenerate in the mammalian central nervous system.

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Faculty Opinions recommendation of Mobility and cycling of synaptic protein-containing vesicles in axonal growth cone filopodia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016257.200727 ◽

2003 ◽

Author(s):

Genevieve Rougon

Keyword(s):

Growth Cone ◽

Axonal Growth ◽

Synaptic Protein ◽

Axonal Growth Cone

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Comparative Analysis of Neural Crest Cell and Axonal Growth Cone Dynamics and Behavior

Intracellular Mechanisms for Neuritogenesis ◽

10.1007/978-0-387-68561-8_13 ◽

2007 ◽

pp. 282-301

Author(s):

Frances Lefcort ◽

Tim O'Connor ◽

Paul M. Kulesa

Keyword(s):

Comparative Analysis ◽

Neural Crest ◽

Growth Cone ◽

Neural Crest Cell ◽

Axonal Growth ◽

Axonal Growth Cone ◽

And Behavior ◽

Crest Cell

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

The Journal of Cell Biology ◽

10.1083/jcb.134.1.205 ◽

1996 ◽

Vol 134 (1) ◽

pp. 205-215 ◽

Cited By ~ 96

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.

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