The dependence receptors DCC and UNC5H as a link between neuronal guidance and survival

被引:67
作者
Mehlen, P [1 ]
Mazelin, L [1 ]
机构
[1] Univ Lyon 1, Apoptosis Differentiat Lab, Equipe Labellisee La Ligue, Mol & Cellular Genet Ctr,CNRS,UMR 5534, F-69622 Villeurbanne, France
关键词
D O I
10.1016/S0248-4900(03)00072-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Netrins are secreted proteins that play a crucial role in neuronal migration and in axon guidance during the development of the nervous system. Netrin-1 has been shown to interact with the transmembrane receptors DCC and UNC5H and these receptors appeared of key importance in mediating the chemotropic activity of netrin-1. Before the discovery of DCC as a netrin-1 receptor, the gene encoding DCC was proposed as a putative tumor suppressor gene because one DCC allele was deleted in roughly 70% of colorectal cancers and its expression was often reduced or absent in colorectal cancer tissues. A putative explanation for such dual roles has recently emerged with the observation that DCC belongs to the growing family of dependence receptors. Such receptors share the property of inducing apoptosis in the absence of ligand, hence creating a cellular state of dependence on the ligand. The other netrin-1 receptors UNC5H were also subsequently proposed to be dependence receptors, suggesting that netrin-1 may not only be a chemotropic factor for neurons but also a survival factor. We describe here netrin-1 and its receptors, together with the molecular signaling pathways initiated upon netrin-1 binding or upon netrin-1 withdrawal leading respectively to axonal/neuronal guidance or cell death induction. We then conclude to the possible roles of DCC and UNC5H pro-apoptotic activities in both nervous system development and tumorigenesis. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
引用
收藏
页码:425 / 436
页数:12
相关论文
共 118 条
[1]   The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein [J].
Ackerman, SL ;
Kozak, LP ;
Przyborski, SA ;
Rund, LA ;
Boyer, BB ;
Knowles, BB .
NATURE, 1997, 386 (6627) :838-842
[2]  
Alcántara S, 2000, DEVELOPMENT, V127, P1359
[3]   The NTR module:: Domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases [J].
Bányai, L ;
Patthy, L .
PROTEIN SCIENCE, 1999, 8 (08) :1636-1642
[4]   DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study [J].
Barratt, PL ;
Seymour, MT ;
Stenning, SP ;
Georgiades, I ;
Walker, C ;
Birbeck, K ;
Quirke, P .
LANCET, 2002, 360 (9343) :1381-1391
[5]  
Bloch-Gallego E, 1999, J NEUROSCI, V19, P4407
[6]   The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease [J].
Bordeaux, MC ;
Forcet, C ;
Granger, L ;
Corset, V ;
Bidaud, C ;
Billaud, M ;
Bredesen, DE ;
Edery, P ;
Mehlen, P .
EMBO JOURNAL, 2000, 19 (15) :4056-4063
[7]   p75NTR and the concept of cellular dependence:: seeing how the other half die [J].
Bredesen, DE ;
Ye, X ;
Tasinato, A ;
Sperandio, S ;
Wang, JJL ;
Assa-Munt, N ;
Rabizadeh, S .
CELL DEATH AND DIFFERENTIATION, 1998, 5 (05) :365-371
[8]  
BREDESEN DE, 2003, IN PRESS PHYS REV
[9]   LOSS OF HETEROZYGOSITY ON CHROMOSOME 18Q IS ASSOCIATED WITH MUSCLE-INVASIVE TRANSITIONAL-CELL CARCINOMA OF THE BLADDER [J].
BREWSTER, SF ;
GINGELL, JC ;
BROWNE, S ;
BROWN, KW .
BRITISH JOURNAL OF CANCER, 1994, 70 (04) :697-700
[10]  
CAJAL R, 1909, HISTOLOGIE SYSTEM NE