Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5509431 | Cellular Signalling | 2017 | 11 Pages |
Abstract
Neurite outgrowth is a critical step for neurogenesis and remodeling synaptic circuitry during neuronal development and regeneration. An immunoglobulin superfamily member, BOC functions as Sonic hedgehog (Shh) coreceptor in canonical and noncanonical Shh signaling in neuronal development and axon outgrowth/guidance. However signaling mechanisms responsible for BOC action during these processes remain unknown. In our previous studies, a multiprotein complex containing BOC and a closely related protein CDO promotes myogenic differentiation through activation of multiple signaling pathways, including non-receptor tyrosine kinase ABL. Given that ABL and Jun. N-terminal kinase (JNK) are implicated in actin cytoskeletal dynamics required for neurogenesis, we investigated the relationship between BOC, ABL and JNK during neuronal differentiation. Here, we demonstrate that BOC and ABL are induced in P19 embryonal carcinoma (EC) cells and cortical neural progenitor cells (NPCs) during neuronal differentiation. BOC-depleted EC cells or Bocâ/â NPCs exhibit impaired neuronal differentiation with shorter neurite formation. BOC interacts with ABL through its putative SH2 binding domain and seems to be phosphorylated in an ABL activity-dependent manner. Unlike wildtype BOC, ABL-binding defective BOC mutants exhibit impaired JNK activation and neuronal differentiation. Finally, Shh treatment enhances JNK activation which is diminished by BOC depletion. These data suggest that BOC interacts with ABL and activates JNK thereby promoting neuronal differentiation and neurite outgrowth.
Keywords
GliEGFNPCNgn1DCCMAP2SH3JLPBOCDcxABLJun N-terminal kinasebFGFITSJnkSH2MAPKglioma-associated oncogeneNeuronal differentiationShhSrc homology domain 2Src homology domain 3deleted in colorectal cancerdoublecortinRetinoic acidNeurite outgrowthRoboEmbryonal carcinoma cellneural progenitor cellConditioned mediumsonic hedgehogepidermal growth factorbasic fibroblast growth factorroundaboutNeurogenin 1CDOmitogen activated protein kinasekinase dead
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Tuan Anh Vuong, Young-Eun Leem, Bok-Geon Kim, Hana Cho, Sang-Jin Lee, Gyu-Un Bae, Jong-Sun Kang,