Regulation of neurite outgrowth by interactions between the scaffolding protein, JNK-associated leucine zipper protein, and neuronal growth-associated protein superior cervical ganglia clone 10.
JLP (JNK-associated leucine zipper protein) is a novel scaffolding protein involved in JNK signaling. Although it is known that JLP is highly expressed in brain, the biological function of JLP in neuronal systems remains unknown. Here, we report a novel interaction between JLP and SCG10 (superior cervical ganglia clone 10), which is a microtubule-destabilizing factor that is essential for neurite outgrowth. Inhibition of endogenous JLP expression using small interference RNA methodology strongly enhanced nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Our results show that JLP negatively regulates NGF-induced neurite outgrowth by decreasing the level of phosphorylated SCG10. Furthermore, inhibition of JNK phosphorylation by a small molecule inhibitor, SP600125, resulted in inhibition of SCG10 phosphorylation and inhibition of neurite growth. Taken together, our results suggest that JLP negatively regulates NGF-induced neurite outgrowth through a sequestering mechanism that results in an attenuation of NGF-induced SCG10 phosphorylation.
Xu
Hua
H
From the Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Dhanasekaran
Danny N
DN
From the Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Lee
Clement M
CM
From the Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140. Electronic address: clement@temple.edu.
Reddy
E Premkumar
EP
From the Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140. Electronic address: reddy@temple.edu.
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008868:Microtubule Proteins; D009154:Mutation; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; D002352:Carrier Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; C512848:Stmn2 protein, rat; C491792:Stmn3 protein, rat; C432165:pyrazolanthrone; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases