PUBLICATION
ZDHHC17 promotes axon outgrowth by regulating TrkA-tubulin complex formation
- Authors
- Shi, W., Wang, F., Gao, M., Yang, Y., Du, Z., Wang, C., Yao, Y., He, K., Chen, X., Hao, A.
- ID
- ZDB-PUB-150802-1
- Date
- 2015
- Source
- Molecular and cellular neurosciences 68: 194-202 (Journal)
- Registered Authors
- Keywords
- Axon outgrowth, ERK1/2, TrkA, Tubulin, ZDHHC17
- MeSH Terms
-
- Acyltransferases/genetics
- Acyltransferases/metabolism*
- Animals
- Axons/drug effects
- Axons/physiology*
- Cells, Cultured
- Disease Models, Animal
- Larva
- MAP Kinase Signaling System/drug effects
- MAP Kinase Signaling System/physiology
- Mice
- Mice, Inbred Strains
- Morpholines/pharmacology
- Motor Neurons/cytology*
- Motor Neurons/drug effects
- Movement Disorders/genetics
- Nerve Growth Factor/pharmacology
- Neural Stem Cells/drug effects
- Neural Stem Cells/physiology
- RNA Interference/physiology
- Rats
- Receptor, trkA/metabolism*
- Spinal Cord/cytology
- Time Factors
- Tubulin/metabolism*
- Zebrafish
- PubMed
- 26232532 Full text @ Mol. Cell Neurosci.
Citation
Shi, W., Wang, F., Gao, M., Yang, Y., Du, Z., Wang, C., Yao, Y., He, K., Chen, X., Hao, A. (2015) ZDHHC17 promotes axon outgrowth by regulating TrkA-tubulin complex formation. Molecular and cellular neurosciences. 68:194-202.
Abstract
Correct axonal growth during nervous system development is critical for synaptic transduction and nervous system function. Proper axon outgrowth relies on a suitable growing environment and the expression of a series of endogenous neuronal factors. However, the mechanisms of these neuronal proteins involved in neuronal development remain unknown. ZDHHC17 is a member of the DHHC (Asp-His-His-Cys)-containing family, a family of highly homologous proteins. Here, we show that loss of function of ZDHHC17 in zebrafish leads to motor dysfunction in 3-day post-fertilization (dpf) larvae. We performed immunolabeling analysis to reveal that mobility dysfunction was due to a significant defect in the axonal outgrowth of spinal motor neurons (SMNs) without affecting neuron generation. In addition, we found a similar phenotype in zdhhc17 siRNA-treated neural stem cells (NSCs) and PC12 cells. Inhibition of zdhhc17 limited neurite outgrowth and branching in both NSCs and PC12. Furthermore, we discovered that the level of phosphorylation of extracellular-regulated kinase (ERK) 1/2, a major downstream effector of tyrosine kinase (TrkA), was largely upregulated in ZDHHC17 overexpressing PC12 cells by a mechanism independent on its palmitoyltransferase (PAT) activity. Specifically, ZDHHC17 is necessary for proper TrkA-tubulin module formation in PC12 cells. These results strongly indicate that ZDHHC17 is essential for correct axon outgrowth in vivo and in vitro. Our findings identify ZDHHC17 as an important upstream factor of ERK1/2 to regulate the interaction between TrkA and tubulin during neuronal development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping