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

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 1; p. 230
• Main Authors: Tan, Dandan, Zhang, Haowen, Deng, Junyao, Liu, Jingmin, Wen, Jinkun, Li, Lixia, Wang, Xianghai, Pan, Mengjie, Hu, Xiaofang, Guo, Jiasong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.01.2020; MDPI
• Subjects: Actin; Animals; Antibodies; Axonogenesis; Cell Differentiation; Cytoskeleton; Dorsal root ganglia; Ganglia, Spinal - metabolism; Gene Knockdown Techniques; glu-tubulin; Glycoproteins; Infections; Katanin - metabolism; Kinases; Laboratory animals; microtubule-severing proteins; neurite outgrowth; Neuronal Outgrowth; Neurons - cytology; Neurons - metabolism; p60-katanin; PC12 Cells; Pheochromocytoma cells; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; rhoA GTP-Binding Protein - metabolism; RhoA protein; rhoa signaling pathway; Signal Transduction; spastin; Spastin - metabolism; Tubulin; Tubulin - metabolism; New York; Grand Island New York; St Louis Missouri; United States > US; China; spastin; Glu-tubulin; microtubule-severing proteins; p60-katanin; neurite outgrowth; RhoA signaling pathway
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9010230

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.