GFRα-4 and the tyrosine kinase Ret form a functional receptor complex for persephin
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- 作者：Yasushi Enokido ; Fred de Sauvage ; Jo-Anne Hongo ; Natalia Ninkina ; Arnon Rosenthal ; Vladimir L. Buchman ; Alun M. Davies
- 关键词：ng> ; MD Bootman and P Lipp ; Calcium – ; a life and death signal ; Nature 395 (1998) ; pp. 645– ; 648.
- 刊名：Current Biology
- 出版年：1998
- 出版时间：10 September 1998
- 年：1998
- 卷：8
- 期：18
- 页码：1019-1022
- 全文大小：212 K
文摘
Glial-cell-line-derived neurotrophic factor (GDNF) [1], neurturin [2] and persephin [3] are structurally related, secreted proteins that are widely expressed in the nervous system and other tissues [1, 2, 3, 4 and 5] and promote the survival of a variety of neurons during development [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12]. GDNF and neurturin signal through multicomponent receptors that consist of the Ret receptor tyrosine kinase and one of two structurally related glycosyl-phosphatidylinositol (GPI)-linked ligand-binding subunits: GFRα-1 is the preferred ligand-binding subunit for GDNF, and GFRα-2 is the preferred ligand-binding subunit for neurturin [13, 14, 15, 16, 17, 18, 19, 20 and 21]. Two additional members of the GFRα family of GPI-linked proteins have recently been cloned: GFRα-3 [21, 22 and 23] and GFRα-4 [24]. We have shown that persephin binds efficiently only to GFRα-4, and labelled persephin is effectively displaced from cells expressing GFRα-4 by persephin but not by GDNF or neurturin. Using microinjection to introduce expression plasmids into cultured neurons, we have also shown that coexpression of Ret with GFRα-4 confers a marked survival response to persephin but not to GDNF or neurturin. These results demonstrate that GFRα-4 is the ligand-binding subunit for persephin and that persephin, like GDNF and neurturin, also requires Ret for signalling.