scholarly journals Plexin-B1/RhoGEF–mediated RhoA activation involves the receptor tyrosine kinase ErbB-2

2004 ◽  
Vol 165 (6) ◽  
pp. 869-880 ◽  
Author(s):  
Jakub M. Swiercz ◽  
Rohini Kuner ◽  
Stefan Offermanns
Keyword(s):  
Tyrosine Kinase ◽  
Growth Cone ◽  
Receptor Tyrosine Kinase ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Axonal Growth ◽  
Dominant Negative ◽  
Growth Cone Collapse ◽  
Rhoa Activation ◽  
Axonal Growth Cone

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.

scholarly journals Unique Responses of Differentiating Neuronal Growth Cones to Inhibitory Cues Presented by Oligodendrocytes

1998 ◽  
Vol 142 (1) ◽  
pp. 191-202 ◽  
Author(s):  
A. Shibata ◽  
M.V. Wright ◽  
S. David ◽  
L. McKerracher ◽  
P.E. Braun ◽  
...  
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Dendritic Growth ◽  
System Development ◽  
Axonal Growth ◽  
Growth Cones ◽  
Nervous System Development ◽  
Environmental Cues ◽  
Growth Cone Collapse ◽  
Neuronal Growth Cones

During central nervous system development, neurons differentiate distinct axonal and dendritic processes whose outgrowth is influenced by environmental cues. Given the known intrinsic differences between axons and dendrites and that little is known about the response of dendrites to inhibitory cues, we tested the hypothesis that outgrowth of differentiating axons and dendrites of hippocampal neurons is differentially influenced by inhibitory environmental cues. A sensitive growth cone behavior assay was used to assess responses of differentiating axonal and dendritic growth cones to oligodendrocytes and oligodendrocyte- derived, myelin-associated glycoprotein (MAG). We report that >90% of axonal growth cones collapsed after contact with oligodendrocytes. None of the encounters between differentiating, MAP-2 positive dendritic growth cones and oligodendrocytes resulted in growth cone collapse. The insensitivity of differentiating dendritic growth cones appears to be acquired since they develop from minor processes whose growth cones are inhibited (nearly 70% collapse) by contact with oligodendrocytes. Recombinant MAG(rMAG)-coated beads caused collapse of 72% of axonal growth cones but only 29% of differentiating dendritic growth cones. Unlike their response to contact with oligodendrocytes, few growth cones of minor processes were inhibited by rMAG-coated beads (20% collapsed). These results reveal the capability of differentiating growth cones of the same neuron to partition the complex molecular terrain they navigate by generating unique responses to particular inhibitory environmental cues.

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

2018 ◽  
Vol 39 (4) ◽  
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.

scholarly journals Rapid changes in the distribution of GAP-43 correlate with the expression of neuronal polarity during normal development and under experimental conditions.

1990 ◽  
Vol 110 (4) ◽  
pp. 1319-1331 ◽  
Author(s):  
K Goslin ◽  
G Banker
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Axonal Growth ◽  
Growth Cones ◽  
Growth Characteristics ◽  
Neuronal Polarity ◽  
Experimental Conditions ◽  
Axonal Growth Cone ◽  
Axonal Transection

Hippocampal neurons growing in culture initially extend several, short minor processes that have the potential to become either axons or dendrites. The first expression of polarity occurs when one of these minor processes begins to elongate rapidly, becoming the axon. Before axonal outgrowth, the growth-associated protein GAP-43 is distributed equally among the growth cones of the minor processes; it is preferentially concentrated in the axonal growth cone once polarity has been established (Goslin, K., D. Schreyer, J. Skene, and G. Banker. 1990. J. Neurosci. 10:588-602). To determine when the selective segregation of GAP-43 begins, we followed individual cells by video microscopy, fixed them as soon as the axon could be distinguished, and localized GAP-43 by immunofluorescence microscopy. Individual minor processes acquired axonal growth characteristics within a period of 30-60 min, and GAP-43 became selectively concentrated to the growth cones of these processes with an equally rapid time course. We also examined changes in the distribution of GAP-43 after transection of the axon. After an axonal transection that is distant from the soma, neuronal polarity is maintained, and the original axon begins to regrow almost immediately. In such cases, GAP-43 became selectively concentrated in the new axonal growth cone within 12-30 min. In contrast, when the axon is transected close to the soma, polarity is lost; the original axon rarely regrows, and there is a significant delay before a new axon emerges. Under these circumstances, GAP-43 accumulated in the new growth cone much more slowly, suggesting that its ongoing selective routing to the axon had been disrupted by the transection. These results demonstrate that the selective segregation of GAP-43 to the growth cone of a single process is closely correlated with the acquisition of axonal growth characteristics and, hence, with the expression of polarity.

Oligodendrocytes repel axons and cause axonal growth cone collapse

1989 ◽  
Vol 92 (1) ◽  
pp. 93-100 ◽  
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.

scholarly journals BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

2017 ◽  
Vol 114 (14) ◽  
pp. E2955-E2964 ◽  
Author(s):  
Ginny G. Farías ◽  
Carlos M. Guardia ◽  
Raffaella De Pace ◽  
Dylan J. Britt ◽  
Juan S. Bonifacino
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Axonal Growth ◽  
General Mechanism ◽  
Cellular Functions ◽  
Axonal Growth Cone ◽  
Polarized Transport

The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.

scholarly journals TRIM31 facilitates K27-linked polyubiquitination of SYK to regulate antifungal immunity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xueer Wang ◽  
Honghai Zhang ◽  
Zhugui Shao ◽  
Wanxin Zhuang ◽  
Chao Sui ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Fungal Pathogen ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Systemic Infection ◽  
Lectin Receptors ◽  
Innate And Adaptive Immunity ◽  
Cytokines And Chemokines

AbstractSpleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

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