title: SH2B1 and IRSp53 proteins promote the formation of dendrites and dendritic branches.
abstract: SH2B1 is an adaptor protein known to enhance neurite outgrowth. In this study, we provide evidence suggesting that the SH2B1 level is increased during in vitro culture of hippocampal neurons, and the β isoform (SH2B1β) is the predominant isoform. The fact that formation of filopodia is prerequisite for neurite initiation suggests that SH2B1 may regulate filopodium formation and thus neurite initiation. To investigate whether SH2B1 may regulate filopodium formation, the effect of SH2B1 and a membrane and actin regulator, IRSp53 (insulin receptor tyrosine kinase substrate p53), is investigated. Overexpressing both SH2B1β and IRSp53 significantly enhances filopodium formation, neurite outgrowth, and branching. Both in vivo and in vitro data show that SH2B1 interacts with IRSp53 in hippocampal neurons. This interaction depends on the N-terminal proline-rich domains of SH2B1. In addition, SH2B1 and IRSp53 co-localize at the plasma membrane, and their levels increase in the Triton X-100-insoluble fraction of developing neurons. These findings suggest that SH2B1-IRSp53 complexes promote the formation of filopodia, neurite initiation, and neuronal branching.
authors.affiliation: From the Institute of Molecular Medicine.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: From the Institute of Molecular Medicine.
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Shih
authors.affiliation: From the Institute of Molecular Medicine.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: From the Institute of Molecular Medicine.
authors.forename: Shao-Jing
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Institute of Molecular and Cellular Biology.
authors.forename: Tian-Neng
authors.initials: TN
authors.lastname: Li
authors.affiliation: Institute of Molecular and Cellular Biology, Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan 30013, China.
authors.forename: Lily Hui-Ching
authors.initials: LH
authors.lastname: Wang
authors.affiliation: From the Institute of Molecular Medicine, Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan 30013, China lchen@life.nthu.edu.tw.
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D003712:Dendrites / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C503229:Baiap2 protein, rat; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C492010:SH2B1 protein, rat
keywords: Cell Biology; Cell Differentiation; Intracellular Trafficking; Membrane Structure; Molecular Cell Biology; Neurite Outgrowth; Neurodifferentiation