デジマ カツフミ   Dejima Katsufumi
  出嶋 克史
   所属   医学部 医学科
   職種   助教
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans.
掲載誌名 正式名:The Journal of biological chemistry
略  称:J Biol Chem
ISSNコード:1083-351X(Electronic)0021-9258(Linking)
巻・号・頁 286(19),17103-11頁
著者・共著者 Dejima Katsufumi, Kanai Makoto I, Akiyama Takuya, Levings Daniel C, Nakato Hiroshi
発行年月 2011/05
概要 We previously proposed a model that DALLY, a Drosophila glypican, acts as a trans co-receptor to regulate BMP signaling in the germ line stem cell niche. To investigate the molecular mechanisms of contact-dependent BMP signaling, we developed novel in vitro assay systems to monitor trans signaling using Drosophila S2 cells. Using immunoblot-based as well as single-cell assay systems, we present evidence that Drosophila glypicans indeed enhance BMP signaling in trans in a contact-dependent manner in vitro. Our analysis showed that heparan sulfate modification is required for the trans co-receptor activity of DALLY. Two BMP-like molecules, Decapentaplegic (DPP) and Glass bottom boat, can mediate trans signaling through a heparan sulfate proteoglycan co-receptor in S2 cells. The in vitro systems reflect the molecular characteristics of heparan sulfate proteoglycan functions observed previously in vivo, such as ligand specificity and biphasic activity dependent on the ligand dosage. In addition, experiments using a DALLY-coated surface suggested that DALLY regulates DPP signaling in trans by its effect on the stability of DPP protein on the surface ofthe contacting cells. Our findings provide the molecular foundation for novel contact-dependent signaling, which defines the physical space of the stem cell niche in vivo.
DOI 10.1074/jbc.M110.208082
文献番号 21454551