Evidence for the Involvement of Lfc and Tctex-1 in Axon Formation

Conde, Cecı́lia; Arias, Cristina; Robin, Maria; Li, Aiqun; Saito, Masaki; Chuang, Jen Zen; Nairn, Angus C.; Sung, Ching Hwa; Cáceres, Alfredo

doi:10.1523/jneurosci.5420-09.2010

Cited by 38 publications

(69 citation statements)

References 41 publications

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“…This process might lead to sustained RhoA activation. Because suppression of GEF-H1 and Rho-kinase expression in cultured neurons induces the formation of multiple axons (49,51,53), this pathway plays critical roles in the "stochastic" neuronal polarization. PKA activates LKB1 and thereby induces A: a local activation-global inhibition mechanism using positive-and negativefeedback signals.…”

Section: Theoretical Basis Of Neuronal Polarizationmentioning

confidence: 99%

Extracellular and Intracellular Signaling for Neuronal Polarity

Namba

Funahashi

Nakamuta

et al. 2015

Physiological Reviews

113

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Neurons are one of the highly polarized cells in the body. One of the fundamental issues in neuroscience is how neurons establish their polarity; therefore, this issue fascinates many scientists. Cultured neurons are useful tools for analyzing the mechanisms of neuronal polarization, and indeed, most of the molecules important in their polarization were identified using culture systems. However, we now know that the process of neuronal polarization in vivo differs in some respects from that in cultured neurons. One of the major differences is their surrounding microenvironment; neurons in vivo can be influenced by extrinsic factors from the microenvironment. Therefore, a major question remains: How are neurons polarized in vivo? Here, we begin by reviewing the process of neuronal polarization in culture conditions and in vivo. We also survey the molecular mechanisms underlying neuronal polarization. Finally, we introduce the theoretical basis of neuronal polarization and the possible involvement of neuronal polarity in disease and traumatic brain injury.

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Section: Theoretical Basis Of Neuronal Polarizationmentioning

confidence: 99%

Extracellular and Intracellular Signaling for Neuronal Polarity

Namba

Funahashi

Nakamuta

et al. 2015

Physiological Reviews

113

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“…Several lines of evidence suggest that RhoA is a negative regulator of neuritogenesis, including axon specification (Da Silva et al, 2003;Conde et al, 2010). A constitutively active form of RhoA inhibits the growth of minor neurite processes in hippocampal neurons (Threadgill et al, 1997;Conde et al, 2010), whereas the inactivation of RhoA enhances neurite extension (Da Silva et al, 2003;Schwamborn and Puschel, 2004). Conditional knockout of RhoA in the midbrain results in the disruption of apical adherens junctions, hyper-proliferation of neural progenitors and massive dysplasia of the brain (Katayama et al, 2011).…”

Section: Rho Family Proteins In Neuronal Polaritymentioning

confidence: 99%

Neuronal polarization

et al. 2015

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Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo.

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“…At present, changes in GEF-H1 after brain ischemia have not been reported in the literature. Several previous studies show that overexpression of GEF-H1 in cultured neurons changes spine length and area (Tolias et al, 2011; Ryan et al, 2005; Conde et al, 2010; Bonnekoh et al, 1990; Dubash et al, 2011). Therefore, upregulation of GEF-H1 protein during the recovery phase may be related to synaptic repairing and formation after brain ischemia.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the GEF-H1 pathway after transient cerebral ischemia

Luo

Roman

Liu

et al. 2015

Experimental Neurology

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The microtubule-dependent GEF-H1 pathway controls synaptic re-networking and overall gene expression via regulating cytoskeleton dynamics. Understanding this pathway after ischemia is essential to developing new therapies for neuronal function recovery. However, how the GEF-H1 pathway is regulated following transient cerebral ischemia remains unknown. This study employed a rat model of transient forebrain ischemia to investigate alterations of the GEF-H1 pathway using Western blotting, confocal and electron microscopy, dephosphorylation analysis, and pull-down assay. The GEF-H1 activity was significantly upregulated by: (i) dephosphorylation and (ii) translocation to synaptic membrane and nuclear structures during the early phase of reperfusion. GEF-H1 protein was then downregulated in the brain regions where neurons were destined to undergo delayed neuronal death, but markedly upregulated in neurons that were resistant to the same episode of cerebral ischemia. Consistently, GTP-RhoA, a GEF-H1 substrate, was significantly upregulated after brain ischemia. Electron microscopy further showed that neuronal microtubules were persistently depolymerized in the brain region where GEF-H1 protein was downregulated after brain ischemia. The results demonstrate that the GEF-H1 activity is significantly upregulated in both vulnerable and resistant brain regions in the early phase of reperfusion. However, GEF-H1 protein is downregulated in the vulnerable neurons but upregulated in the ischemic resistant neurons during the recovery phase after ischemia. The initial upregulation of GEF-H1 activity may contribute to excitotoxicity, whereas the late upregulation of GEF-H1 protein may promote neuroplasticity after brain ischemia.

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Evidence for the Involvement of Lfc and Tctex-1 in Axon Formation

Cited by 38 publications

References 41 publications

Extracellular and Intracellular Signaling for Neuronal Polarity

Extracellular and Intracellular Signaling for Neuronal Polarity

Neuronal polarization

Upregulation of the GEF-H1 pathway after transient cerebral ischemia

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