期刊
MOLECULAR NEUROBIOLOGY
卷 53, 期 10, 页码 6594-6607出版社
HUMANA PRESS INC
DOI: 10.1007/s12035-015-9550-2
关键词
Diras1; Neurite outgrowth; Rac1; Trigeminal ganglion; Zebrafish
资金
- Ministry of Science and Technology of Taiwan [MOST-103-2311-B-040-001]
- Zebrafish Core in Academia Sinica (ZCAS), Institute of Cellular and Organismic Biology (ICOB) from National Science Council (NSC) [NSC-103-2321-B-001-050]
- National Health Research Institute (NHRI) from National Science Council (NSC) [100-2321-B-400-003]
- National Science Council
- Ministry of Education
- Chung Shan Medical University
The small GTPase Ras superfamily regulates several neuronal functions including neurite outgrowth and neuron proliferation. In this study, zebrafish diras1a and diras1b were identified and were found to be mainly expressed in the central nervous system and dorsal neuron ganglion. Overexpression of green fluorescent protein (GFP)-diras1a or GFP-diras1b triggered neurite outgrowth of Neuro-2a cells. The wild types, but not the C terminus truncated forms, of diras1a and diras1b elevated the protein level of Ras-related C3 botulinum toxin substrate 1 (Rac1) and downregulated Ras homologous member A (RhoA) expression. Glutathione S-transferase (GST) pull-down assay also revealed that diras1a and diras1b enhanced Rac1 activity. Interfering with Rac1, Pak1, or cyclin-dependent kinase 5 (CDK5) activity or with the Arp2/3 inhibitor prevented diras1a and diras1b from mediating the neurite outgrowth effects. In the zebrafish model, knockdown of diras1a and/or diras1b by morpholino antisense oligonucleotides not only reduced axon guidance but also caused the loss of trigeminal ganglion without affecting the precursor markers, such as ngn1 and neuroD. Co-injection with messenger RNA (mRNA) derived from mouse diras1 or constitutively active human Rac1 restored the population of trigeminal ganglion. In conclusion, we provided preliminary evidence that diras1 is involved in neurite outgrowth and maintains the number of trigeminal ganglions through the Rac1-dependent pathway.
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