title: L1 modulates PKD1 phosphorylation in cerebellar granule neurons.
abstract: The neural cell adhesion molecule L1 (L1CAM) is crucial for the development of the nervous system, with an essential role in regulating multiple cellular activities. Protein kinase D1 (PKD1) serves as a key kinase given its diverse array of functions within the cell. Here, we investigated various aspects of the functional relationship between L1 and phosphorylated PKD1 (pPKD1) in cerebellar granule neurons. To study the relationship between L1 and PKD1 phosphorylation, human cerebellar tissue microarrays were subject to immunofluorescence staining. We observed a positive correlation between L1 protein levels and PKD1 phosphorylation. In addition, L1 also co-localized with pPKD1. To analyze the regulatory role of L1 on PKD1 phosphorylation, primary mouse cerebellar granule neurons were treated with various concentrations of rL1 for 48 h. Using Western blot, we revealed that L1 significantly increased PKD1 phosphorylation compared with vehicle control, with the maximal effect observed at 5 nM. ERK1/2 phosphorylation was significantly increased by 2.5 nM and 10nM L1, with no apparent change in SRC phosphorylation. However, SRC expression was markedly reduced by 10nM rL1. AKT1 expression and phosphorylation levels were significantly increased by rL1, with the maximal effect observed at 2.5 and 5 nM, respectively. Our combined data revealed a positive relationship between L1 and pPKD1 in both cultured cerebellar neurons and human cerebellar tissue, suggesting that L1 functions in the modulation of PKD1 phosphorylation.
authors.affiliation: Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Rd, Jinping District, Shantou, Guangdong Province 515041, PR China.
authors.forename: Shuang-xi
authors.initials: SX
authors.lastname: Chen
authors.affiliation: Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Rd, Jinping District, Shantou, Guangdong Province 515041, PR China.
authors.forename: Cheng-liang
authors.initials: CL
authors.lastname: Hu
authors.affiliation: Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Rd, Jinping District, Shantou, Guangdong Province 515041, PR China.
authors.forename: Yong-hong
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Rd, Jinping District, Shantou, Guangdong Province 515041, PR China. Electronic address: neuromancn@aliyun.com.
authors.forename: Wei-jiang
authors.initials: WJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D039841:Leukocyte L1 Antigen Complex; D011493:Protein Kinase C; D050396:TRPP Cation Channels; C089212:protein kinase D
keywords: Cerebellar granule neurons (CGNs); L1CAM; PKD1 phosphorylation