title: Sur8/Shoc2 involves both inhibition of differentiation and maintenance of self-renewal of neural progenitor cells via modulation of extracellular signal-regulated kinase signaling.
abstract: Sur8/Shoc2 is a scaffold protein that regulates the Ras-extracellular signal-regulated kinase (ERK) pathway. However, the roles of Sur8 in cellular physiologies are poorly understood. In this study, Sur8 was severely repressed in the course of neural progenitor cell (NPC) differentiation in the cerebral cortex of developing rat embryos. Similarly, Sur8 was also critically reduced in cultured NPCs, which were induced differentiation by removal of basic fibroblast growth factor (bFGF). Sur8 regulation occurs at the protein level rather than at the mRNA level as revealed by both in situ hybridization and reverse transcriptase polymerase chain reaction analyses. The role of Sur8 in NPC differentiation was confirmed by lentivirus-mediated Sur8 knockdown, which resulted in increased differentiation, whereas exogenous expression of Sur8 inhibited differentiation. Contrastingly, NPC proliferation was promoted by overexpression, but was suppressed by Sur8 knockdown. The role of Sur8 as an antidifferentiation factor in the developing rat brain was confirmed by an ex vivo embryo culture system combined with the lentivirus-mediated Sur8 knockdown. The numbers and sizes of neurospheres were reduced, but neuronal outgrowth was enhanced by the Sur8 knockdown. The Ras-ERK pathway is involved in Sur8-mediated regulations of differentiation, as the treatment of ERK kinase (MEK) inhibitors blocks the effects of Sur8. The regulations of NPCs' differentiation and proliferation by the Ras-ERK pathway were also shown by the rescues of the effects of bFGF depletion, neuronal differentiation, and antiproliferation by epidermal growth factor. In summary, Sur8 is an antidifferentiation factor that stimulates proliferation for maintenance of self-renewal in NPCs via modulation of the Ras-ERK pathway.
authors: Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors: Byoung-San
authors: BS
authors: Moon
authors: Hyun-Yi
authors: HY
authors: Kim
authors: Mi-Yeon
authors: MY
authors: Kim
authors: Dong-Hwa
authors: DH
authors: Yang
authors: Jong-Min
authors: JM
authors: Lee
authors: Kyoung-Won
authors: KW
authors: Cho
authors: Han-Sung
authors: HS
authors: Jung
authors: Kang-Yell
authors: KY
authors: Choi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007976:Leupeptins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C568887:Shoc2 protein, rat; D016222:Fibroblast Growth Factor 2; C063261:acetylleucyl-leucyl-norleucinal; D048049:Extracellular Signal-Regulated MAP Kinases