The immune molecule CD3zeta and its downstream effectors ZAP-70/Syk mediate ephrin signaling in neurons to regulate early neuritogenesis

被引:12
作者
Angibaud, Julie [2 ,3 ]
Louveau, Antoine [2 ,3 ]
Baudouin, Stephane J. [2 ,3 ]
Nerriere-Daguin, Veronique [2 ,3 ]
Evain, Sarah [2 ,3 ]
Bonnamain, Virginie [2 ,3 ]
Hulin, Philippe [4 ]
Csaba, Zsolt [5 ]
Dournaud, Pascal [5 ]
Thinard, Reynald [2 ,3 ]
Naveilhan, Philippe [2 ,3 ]
Noraz, Nelly [6 ,7 ]
Pellier-Monnin, Veronique [6 ,7 ]
Boudin, Helene [1 ,2 ,3 ]
机构
[1] INSERM, ITUN, U643, F-44093 Nantes 01, France
[2] CHU Nantes, ITUN, Inst Transplantat & Rech Transplantat, F-44035 Nantes 01, France
[3] Univ Nantes, Fac Med, Nantes, France
[4] Univ MicroPICell, Cellular & Tissular Imaging Core Facil Nantes, IFR26, Nantes, France
[5] INSERM, UMR 676, Paris, France
[6] INSERM, F-69008 Lyon, France
[7] Univ Lyon 1, UMR S842, F-69365 Lyon, France
关键词
ephrin; filopodia; growth cone; neuronal differentiation; protein tyrosine kinase; Rho-GEF; SYNAPTIC PLASTICITY; ACTIN CYTOSKELETON; NEURAL DEVELOPMENT; NEURITE OUTGROWTH; PROTEIN CD3-ZETA; AXON GUIDANCE; CELL; ACTIVATION; EPHA4; VAV;
D O I
10.1111/j.1471-4159.2011.07469.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies have highlighted the key role of the immune protein CD3 zeta in the maturation of neuronal circuits in the CNS. Yet, the upstream signals that might recruit and activate CD3 zeta in neurons are still unknown. In this study, we show that CD3 zeta functions early in neuronal development and we identify ephrinA1-dependent EphA4 receptor activation as an upstream regulator of CD3 zeta. When newly born neurons are still spherical, before neurite extension, we found a transient CD3 zeta aggregation at the cell periphery matching the initiation site of the future neurite. This accumulation of CD3 zeta correlated with a stimulatory effect on filopodia extension via a Rho-GEF Vav2 pathway and a repression of neurite outgrowth. Conversely, cultured neurons lacking CD3 zeta isolated from CD3 zeta(-/-) mice showed a decreased number of filopodia and an enhanced neurite number. Stimulation with ephrinA1 induces the translocation of both CD3 zeta and its activated effector molecules, ZAP-70/Syk tyrosine kinases, to EphA4 receptor clusters. EphrinA1-induced growth cone collapse was abrogated in CD3 zeta(-/-) neurons and was markedly reduced by ZAP-70/Syk inhibition. Moreover, ephrinA1-induced ZAP-70/Syk activation was inhibited in CD3 zeta(-/-) neurons. Altogether, our data suggest that CD3 zeta mediates the ZAP-70/Syk kinase activation triggered by ephrinA-activated pathway to regulate early neuronal morphogenesis.
引用
收藏
页码:708 / 722
页数:15
相关论文
共 59 条
[41]   T-cell receptor signal transmission: who gives an ITAM? [J].
Pitcher, LA ;
van Oers, NSC .
TRENDS IN IMMUNOLOGY, 2003, 24 (10) :554-560
[42]   Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2 [J].
Raab, M ;
daSilva, AJ ;
Findell, PR ;
Rudd, CE .
IMMUNITY, 1997, 6 (02) :155-164
[43]   The EphA4 receptor regulates neuronal morphology through SPAR-mediated inactivation of Rap GTPases [J].
Richter, Melanie ;
Murai, Keith K. ;
Bourgin, Caroline ;
Pak, Daniel T. ;
Pasquale, Elena B. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (51) :14205-14215
[44]   IDENTIFICATION OF THE COMPONENTS OF THE MURINE T-CELL ANTIGEN RECEPTOR COMPLEX [J].
SAMELSON, LE ;
HARFORD, JB ;
KLAUSNER, RD .
CELL, 1985, 43 (01) :223-231
[45]   Cell surface antigens on rat neural progenitors and characterization of the CD3(+)/CD3(-) cell populations [J].
Sergent-Tanguy, Solene ;
Veziers, Joelle ;
Bonnamain, Virginie ;
Boudin, Helene ;
Neveu, Isabelle ;
Naveilhan, Philippe .
DIFFERENTIATION, 2006, 74 (9-10) :530-541
[46]   EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin [J].
Shamah, SM ;
Lin, MZ ;
Goldberg, JL ;
Estrach, S ;
Sahin, M ;
Hu, L ;
Bazalakova, M ;
Neve, RL ;
Corfas, G ;
Debant, A ;
Greenberg, ME .
CELL, 2001, 105 (02) :233-244
[47]   α2-chimaerin interacts with EphA4 and regulates EphA4-dependent growth cone collapse [J].
Shi, Lei ;
Fu, Wing-Yu ;
Hung, Kwok-Wang ;
Porchetta, Cassandra ;
Hall, Christine ;
Fu, Amy K. Y. ;
Ip, Nancy Y. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (41) :16347-16352
[48]   MHC class I expression and synaptic plasticity after nerve lesion [J].
Thams, Sebastian ;
Oliveira, Alexandre ;
Cullheim, Staffan .
BRAIN RESEARCH REVIEWS, 2008, 57 (01) :265-269
[49]  
Tsuchihashi N, 2000, EUR J IMMUNOL, V30, P1785, DOI 10.1002/1521-4141(200006)30:6<1785::AID-IMMU1785>3.0.CO
[50]  
2-T