Leucine-Rich Glioma Inactivated 3 Induces Neurite Outgrowth Through Akt and Focal Adhesion Kinase

Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein that belongs to LGI/epitempin family. LGI3 is highly expressed in brain in a transcriptionally and developmentally regulated manner. Here we found that LGI3 induced neurite outgrowth in Neuro-2a cells and dorsal root ganglia explants. LG...

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Bibliographic Details
Published in:Neurochemical research 2010-05, Vol.35 (5), p.789-796
Main Authors: Park, Woo-Jae, Lim, Yun Young, Kwon, Nyoun Soo, Baek, Kwang Jin, Kim, Dong-Seok, Yun, Hye-Young
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Line, Tumor
Chromones - pharmacology
Focal Adhesion Protein-Tyrosine Kinases - physiology
Ganglia, Spinal - growth & development
Mice
Morpholines - pharmacology
Nerve Tissue Proteins - physiology
Neurites - drug effects
Neurites - physiology
Neurochemistry
Neurology
Neurosciences
Original Paper
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - physiology
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Summary:Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein that belongs to LGI/epitempin family. LGI3 is highly expressed in brain in a transcriptionally and developmentally regulated manner. Here we found that LGI3 induced neurite outgrowth in Neuro-2a cells and dorsal root ganglia explants. LGI3 treatment or overexpression increased neurite outgrowth and knockdown of LGI3 by siRNA had opposite effect. LGI3 treatment increased phosphorylation of Akt and a 125-kDa protein. Immunoprecipitation identified the 125-kDa protein as focal adhesion kinase (FAK). LGI3 overexpression increased phospho-Akt, phospho-FAK and FAK protein. Inhibition of Akt activation by PI3 kinase inhibitor attenuated LGI3-induced FAK phosphorylation and neurite outgrowth. Taken together, we propose that LGI3 is a neuritogenic factor whose signaling pathway involves Akt-mediated FAK activation.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-010-0136-0