scholarly journals RhoA-GTPase Modulates Neurite Outgrowth by Regulating the Expression of Spastin and p60-Katanin

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 230
Author(s):  
Dandan Tan ◽  
Haowen Zhang ◽  
Junyao Deng ◽  
Jingmin Liu ◽  
Jinkun Wen ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Signaling Pathway ◽  
Lentiviral Vector ◽  
Coiled Coil ◽  
Current Data ◽  
Microtubule Dynamics ◽  
Microtubule Severing ◽  
Downstream Effector ◽  
Rhoa Gtpase ◽  
Rhoa Signaling

RhoA-GTPase (RhoA) is widely regarded as a key molecular switch to inhibit neurite outgrowth by rigidifying the actin cytoskeleton. However, during neurite outgrowth, whether and how microtubule dynamics are regulated by RhoA remains to be elucidated. Herein, CT04 and Y27632 were used to inactivate RhoA and its downstream effector Rho-associated coiled coil-forming kinase (ROCK), while the RhoAQ63L lentiviral vector was utilized to overexpress the constitutively activated RhoA in dorsal root ganglion (DRG) neurons or neuronal differentiated PC12 cells. The current data illustrate that the RhoA signaling pathway negatively modulates neurite outgrowth and elevates the expression of Glu-tubulin (a marker for a stabilized microtubule). Meanwhile, the microtubule-severing proteins spastin and p60-katanin were downregulated by the RhoA signaling pathway. When spastin and p60-katanin were knocked down, the effects of RhoA inhibition on neurite outgrowth were significantly reversed. Taken together, this study demonstrates that the RhoA pathway-mediated inhibition of neurite outgrowth is not only related to the modulation of microfilament dynamics but is also attributable to the regulation of the expression of spastin and p60-katanin and thus influences microtubule dynamics.

Spastin Interacts with CRMP2 to Regulate Neurite Outgrowth by Controlling Microtubule Dynamics through Phosphorylation Modifications

2020 ◽  
Vol 19 ◽  
Author(s):  
Sumei Li ◽  
Jifeng Zhang ◽  
Jiaqi Zhang ◽  
Jiong Li ◽  
Longfei Cheng ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
Phosphorylation Site ◽  
Microtubule Dynamics ◽  
Microtubule Assembly ◽  
C Terminus ◽  
Mediator Protein ◽  
Branch Formation

Aims: Our work aims to revealing the underlying microtubule mechanism of neurites outgrowth during neuronal development, and also proposes a feasible intervention pathway for reconstructing neural network connections after nerve injury. Background: Microtubule polymerization and severing are the basis for the neurite outgrowth and branch formation. Collapsin response mediator protein 2 (CRMP2) regulates axonal growth and branching as a binding partner of the tubulin heterodimer to promote microtubule assembly. And spastin participates in the growth and regeneration of neurites by severing microtubules into small segments. However, how CRMP2 and spastin cooperate to regulate neurite outgrowth by controlling the microtubule dynamics needs to be elucidated. Objective: To explore whether neurite outgrowth was mediated by coordination of CRMP2 and spastin. Method: Hippocampal neurons were cultured in vitro in 24-well culture plates for 4 days before being used to perform the transfection. Calcium phosphate was used to transfect the CRMP2 and spastin constructs and their control into the neurons. An interaction between CRMP2 and spastin was examined by using pull down, CoIP and immunofluorescence colocalization assays. And immunostaining was also performed to determine the morphology of neurites. Result: We first demonstrated that CRMP2 interacted with spastin to promote the neurite outgrowth and branch formation. Furthermore, our results identified that phosphorylation modification failed to alter the binding affinities of CRMP2 for spastin, but inhibited their binding to microtubules. CRMP2 interacted with the MTBD domain of spastin via its C-terminus, and blocking the binding sites of them inhibited the outgrowth and branch formation of neurites. In addition, we confirmed one phosphorylation site S210 at spastin in hippocampal neurons and phosphorylation spastin at site S210 promoted the neurite outgrowth but not branch formation by remodeling microtubules. Conclusion: Taken together, our data demonstrated that the interaction of CRMP2 and spastin is required for neurite outgrowth and branch formation and their interaction is not regulated by their phosphorylation.

scholarly journals Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway

2017 ◽  
Vol 18 (10) ◽  
pp. 783-791 ◽  
Author(s):  
Xiao Huaitong ◽  
Feng Yuanyong ◽  
Tao Yueqin ◽  
Zhao Peng ◽  
Shang Wei ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Oral Cancer Cells ◽  
Rhoa Signaling

scholarly journals Human cytomegalovirus exploits TACC3 to control microtubule dynamics and late stages of infection

2021 ◽  
Author(s):  
Colleen Furey ◽  
Helen Astar ◽  
Derek Walsh
Keyword(s):  
Virus Replication ◽  
Human Cytomegalovirus ◽  
Coiled Coil ◽  
Microtubule Dynamics ◽  
Replication Cycle ◽  
Microtubule Organizing Center ◽  
Viral Particles ◽  
Organizing Center ◽  
Assembly Compartment ◽  
Late Stages

While it is well established that microtubules (MTs) facilitate various stages of virus replication, how viruses actively control MT dynamics and functions remains less-well understood. Recent work has begun to reveal how several viruses exploit End-Binding (EB) proteins and their associated microtubule plus-end tracking proteins (+TIPs), in particular to enable loading of viral particles onto MTs for retrograde transport during early stages of infection. But distinct from other viruses studied to date, at mid-to-late stages of its unusually protracted replication cycle human cytomegalovirus (HCMV) increases the expression of all three EB family members. This occurs coincident with the formation of a unique structure termed the Assembly Compartment (AC), which serves as a Golgi-derived MT organizing center. Together, the AC and distinct EB proteins enable HCMV to increase the formation of dynamic and acetylated microtubule subsets to regulate distinct aspects of the viral replication cycle. Here, we reveal that HCMV also exploits EB-independent +TIP pathways by specifically increasing the expression of Transforming Acidic Coiled Coil protein 3 (TACC3) to recruit the MT polymerase, chTOG from initial sites of MT nucleation in the AC out into the cytosol, thereby increasing dynamic MT growth. Preventing TACC3 increases or depleting chTOG impaired MT polymerization, resulting in defects in early versus late endosome organization in and around the AC as well as defects in viral trafficking and spread. Our findings provide the first example of a virus that actively exploits EB-independent +TIP pathways to regulate MT dynamics and control late stages of virus replication. Importance Diverse viruses rely on host cell microtubule networks in order to transport viral particles within the dense cytoplasmic environment and to control the broader architecture of the cell to facilitate their replication. Yet precisely how viruses regulate the dynamic behavior and function of microtubule filaments remains poorly defined. We recently showed that the Assembly Compartment (AC) formed by human cytomegalovirus (HCMV) acts as a Golgi-derived microtubule organizing center. Here, we show that at mid-to-late stages of infection, HCMV increases the expression of Transforming Acidic Coiled Coil protein 3 (TACC3) in order to control the localization of the microtubule polymerase, chTOG. This in turn enables HCMV to generate dynamic microtubule subsets that organize endocytic vesicles in and around the AC and facilitate the transport of new viral particles released into the cytosol. Our findings reveal the first instance of viral targeting of TACC3 to control microtubule dynamics and virus spread.

scholarly journals Emodin Successfully Inhibited Invasion of Brucella abortus Via Modulting Adherence, Microtubule Dynamics and ERK Signaling Pathway in RAW 264.7 Cells

2018 ◽  
Vol 28 (10) ◽  
pp. 1723-1729 ◽  
Author(s):  
Tran Xuan Ngoc Huy ◽  
Alisha Wehdnesday Bernardo Reyes ◽  
Huynh Tan Hop ◽  
Lauren Togonon Arayan ◽  
Vu Hai Son ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Brucella Abortus ◽  
Microtubule Dynamics ◽  
Erk Signaling ◽  
Raw 264.7 Cells ◽  
Raw 264.7

scholarly journals The Role and Mechanism of AMIGO3 in the Formation of Aberrant Neural Circuits After Status Convulsion in Immature Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Xue Li ◽  
Yanan Pan ◽  
Jianxiong Gui ◽  
Zhixu Fang ◽  
Dishu Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Axonal Regeneration ◽  
Neural Circuits ◽  
Axon Growth ◽  
Demyelinating Diseases ◽  
Reading Frame ◽  
Myelin Sheaths ◽  
Transmission Electron ◽  
Rhoa Signaling ◽  
Myelin Basic Protein Expression

Leucine rich repeat and immunoglobulin-like domain-containing protein 1 (Lingo-1) has gained considerable interest as a potential therapy for demyelinating diseases since it inhibits axonal regeneration and myelin production. However, the results of clinical trials targeted at Lingo-1 have been unsatisfactory. Amphoterin-induced gene and open reading frame-3 (AMIGO3), which is an analog of Lingo-1, might be an alternative therapeutic target for brain damage. In the present study, we investigated the effects of AMIGO3 on neural circuits in immature mice after status convulsion (SC) induced by kainic acid. The expression of both AMIGO3 and Lingo-1 was significantly increased after SC, with levels maintained to 20 days after SC. Following SC, transmission electron microscopy revealed the impaired microstructure of myelin sheaths and Western blot analysis showed a decrease in myelin basic protein expression, and this damage was alleviated by downregulation of AMIGO3 expression. The ROCK/RhoA signaling pathway was inhibited at 20 days after SC by downregulating AMIGO3 expression. These results indicate that AMIGO3 plays important roles in seizure-induced damage of myelin sheaths as well as axon growth and synaptic plasticity via the ROCK/RhoA signaling pathway.

Insulin attenuates arsenic-induced neurite outgrowth impairments by activating the PI3K/Akt/SIRT1 signaling pathway

2015 ◽  
Vol 236 (3) ◽  
pp. 138-144 ◽  
Author(s):  
Apichaya Niyomchan ◽  
Piyajit Watcharasit ◽  
Daranee Visitnonthachai ◽  
Benjaporn Homkajorn ◽  
Apinya Thiantanawat ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Signaling Pathway

Spastin Interacts with CRMP5 to Promote Neurite Outgrowth by Controlling the Microtubule Dynamics

2018 ◽  
Vol 78 (12) ◽  
pp. 1191-1205 ◽  
Author(s):  
Zhisheng Ji ◽  
Guowei Zhang ◽  
Li Chen ◽  
Jiong Li ◽  
Yuhao Yang ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Microtubule Dynamics ◽  
Promote Neurite Outgrowth
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