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 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 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.

scholarly journals Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration

2020 ◽  
Vol 14 ◽  
Author(s):  
Michael J. Rigby ◽  
Timothy M. Gomez ◽  
Luigi Puglielli
Keyword(s):  
Glial Cell ◽  
Growth Cone ◽  
Axonal Growth ◽  
Axonal Growth Cone

scholarly journals Protein interacting with NIMA (never in mitosis A)-1 regulates axonal growth cone adhesion and spreading through myristoylated alanine-rich C kinase substrate isomerization

2016 ◽  
Vol 137 (5) ◽  
pp. 744-755 ◽  
Author(s):  
Lucas J. Sosa ◽  
James S. Malter ◽  
Jie Hu ◽  
Florentyna Bustos Plonka ◽  
Mariana Oksdath ◽  
...  
Keyword(s):  
Growth Cone ◽  
Axonal Growth ◽  
Kinase Substrate ◽  
Axonal Growth Cone

Transduction of Inhibitory Signals by the Axonal Growth Cone

2000 ◽  
pp. 131-153
Author(s):  
Li-Hsien Wang ◽  
Alyson Fournier ◽  
Fumio Nakamura ◽  
Takuya Takahashi ◽  
Robert G. Kalb ◽  
...  
Keyword(s):  
Growth Cone ◽  
Axonal Growth ◽  
Axonal Growth Cone

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.

Sign in / Sign up

Export Citation Format

Share Document