title: SH2B1β regulates N-cadherin levels, cell-cell adhesion and nerve growth factor-induced neurite initiation.
abstract: Little is known regarding the role of inter-cellular interaction during neuronal differentiation. Homophilic N-cadherin engagement between cells contributes to neuronal migration. However, its function in neurite initiation is not clear. In this study, we provide the first evidence that the adaptor protein SH2B1β regulated N-cadherin levels and neurite initiation. Overexpression of SH2B1β reduces N-cadherin levels and increased phosphotyrosine 654 β-catenin, leading to increased nerve growth factor-induced neurite initiation in PC12 cells, an established model for neuronal differentiation. In contrast, overexpression of the dominant-negative mutant SH2B1β(R555E) increases N-cadherin expression, cell-cell aggregation, and reduces neurite initiation. Moreover, SH2B1β binds directly or indirectly to N-cadherin indicative of its involvement in regulating the levels of N-cadherin. Taken together, these findings provide significant new insights into how N-cadherin-mediated inter-cellular interactions may influence neurite initiation and how SH2B1β may regulate these processes.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Tien-Cheng
authors.initials: TC
authors.lastname: Wang
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Li
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Chen
authors.forename: Ching-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Wu
authors.forename: Nan-Yuan
authors.initials: NY
authors.lastname: Teng
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002522:Chlorocebus aethiops; D047908:Intracellular Signaling Peptides and Proteins; D020932:Nerve Growth Factor / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis; D016716:PC12 Cells; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C492010:SH2B1 protein, rat; D051176:beta Catenin; D019000:Phosphotyrosine; D020932:Nerve Growth Factor