Phosphorylation of the Zebrafish M6Ab at Serine 263 Contributes to Filopodium Formation in PC12 Cells and Neurite Outgrowth in Zebrafish Embryos
- Authors
- Huang, K.Y., Chen, G.D., Cheng, C.H., Liao, K.Y., Hung, C.C., Chang, G.D., Hwang, P.P., Lin, S.Y., Tsai, M.C., Khoo, K.H., Lee, M.T., and Huang, C.J.
- ID
- ZDB-PUB-111114-6
- Date
- 2011
- Source
- PLoS One 6(10): e26461 (Journal)
- Registered Authors
- Hwang, Pung Pung
- Keywords
- none
- MeSH Terms
-
- Phosphorylation/drug effects
- Animals
- MAP Kinase Kinase 1/metabolism
- Amino Acid Sequence
- Embryo, Nonmammalian/cytology*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Pseudopodia/drug effects
- Pseudopodia/metabolism*
- Chlorocebus aethiops
- PC12 Cells
- Rats
- Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
- Glycoproteins/chemistry
- Glycoproteins/genetics
- Glycoproteins/metabolism
- Molecular Sequence Data
- Serine/metabolism*
- Neurites/drug effects
- Neurites/metabolism*
- Nerve Growth Factor/pharmacology
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Membrane Glycoproteins/chemistry*
- Membrane Glycoproteins/genetics
- Membrane Glycoproteins/metabolism*
- Zebrafish/embryology*
- Signal Transduction/drug effects
- COS Cells
- MAP Kinase Kinase 2/metabolism
- PubMed
- 22028883 Full text @ PLoS One
Background
Mammalian M6A, a member of the proteolipid protein (PLP/DM20) family expressed in neurons, was first isolated by expression cloning with a monoclonal antibody. Overexpression of M6A was shown to induce filopodium formation in neuronal cells; however, the underlying mechanism of is largely unknown. Possibly due to gene duplication, there are two M6A paralogs, M6Aa and M6Ab, in the zebrafish genome. In the present study, we used the zebrafish as a model system to investigate the role of zebrafish M6Ab in filopodium formation in PC12 cells and neurite outgrowth in zebrafish embryos.
Methodology/Principal Findings
We demonstrated that zebrafish M6Ab promoted extensive filopodium formation in NGF-treated PC12 cells, which is similar to the function of mammalian M6A. Phosphorylation at serine 263 of zebrafish M6Ab contributed to this induction. Transfection of the S263A mutant protein greatly reduced filopodium formation in PC12 cells. In zebrafish embryos, only S263D could induce neurite outgrowth.
Conclusions/Significance
Our results reveal that the phosphorylation status of zebrafish M6Ab at serine 263 is critical for its role in regulating filopodium formation and neurite outgrowth.