ヤマウチ　カヅヨ   YAMAUCHI Kadzuyo   山内　かづ代    所属   医学部 医学科    職種   評議員
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Low-density lipoprotein receptor related protein-1 (LRP1)-dependent cell signaling promotes neurotrophic activity in embryonic sensory neurons.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：(1932-6203)1932-6203(Linking)
掲載区分	国外
巻・号・頁	8(9),pp.e75497
著者・共著者	Yamauchi Kazuyo, Yamauchi Tomonori, Mantuano Elisabetta, Murakami Kenichi, Henry Kenneth, Takahashi Kazuhisa, Campana Wendy Marie
発行年月	2013
概要	Developing sensory neurons require neurotrophic support for survival, neurite outgrowth and myelination. The low-density lipoprotein receptor-related protein-1 (LRP1) transactivates Trk receptors and thereby functions as a putative neurotrophin. Herein, we show that LRP1 is abundantly expressed in developing dorsal root ganglia (DRG) and that LRP1-dependent cell signaling supports survival, neurite extension and receptivity to Schwann cells even in the absence of neurotrophins. Cultured embryonic DRG neurons (E15) were treated with previously characterized LRP1 ligands, LRP1-receptor binding domain of α2-macroglobulin (RBD), hemopexin domain of MMP-9 (PEX) or controls (GST) for two weeks. These structurally diverse LRP1 ligands significantly activated and sustained extracellular signal-regulated kinases (ERK1/2) 5-fold (p<0.05), increased expression of growth-associated protein-43(GAP43) 15-fold (P<0.01), and increased neurite outgrowth 20-fold (P<0.01). Primary sensory neurons treated with LRP1 ligands survived > 2 weeks in vitro, to an extent equaling NGF, a finding associated with canonical signaling mechanisms and blockade of caspase-3 cleavage. Furthermore, LRP1-induced neurite sprouting was mediated by Src-family kinase (SFK) activation, suggesting transactivation of Trk receptors. Co-cultures of primary embryonic neurons and Schwann cells showed that LRP1 agonists promoted axonal receptivity to myelination to Schwann cells. Collectively, these findings identify LRP1 as a novel and perhaps essential trophic molecule for sensory neuronal survival and development.
DOI	10.1371/journal.pone.0075497
PMID	24086544