Signalling events regulating the retrograde axonal transport of 125I-β Nerve growth factor in vivo

被引:38
作者
Reynolds, AJ [1 ]
Bartlett, SE [1 ]
Hendry, IA [1 ]
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, Div Neurosci, Canberra, ACT 2601, Australia
关键词
phosphoinositide-3; kinase; PI3-kinase; wortmannin; LY294002; retrograde axonal transport; nerve growth factor;
D O I
10.1016/S0006-8993(98)00396-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The molecular mechanisms regulating the retrograde axonal transport of nerve growth factor (NGF) are currently unknown. This study identifies some of the signalling events involved. The phosphoinositide 3-kinase (PI3-kinase) inhibitor wortmannin (1 nmol/eye) irreversibly inhibits the amount of I-125 - beta NGF retrogradely transported in both sensory and sympathetic neurons. Another PI3-kinase inhibitor LY294002 (100 nmol/eye) also inhibited I-125 - beta NGF retrograde transport in sensory neurons. The pp70(S6K) inhibitor rapamycin (1 mu mol/eye) had the same effect, inhibiting I-125 - beta NGF transport only in sensory neurons. The cPLA(2) inhibitor AACOCF(3) (10 nmol/eye) had no effect on I-125 - beta NGF transport in either sensory or sympathetic neurons. The TrkA receptor tyrosine kinase inhibitor AG-879 (10 nmol/eye) reduced I-125 - beta NGF transport by approximately 50% in both sensory and sympathetic neurons. Cytochalasin D (2 nmol/eye), a disrupter of actin filaments and the dynein ATPase inhibitor erythro-9-[3-(2-hydroxynonyl)]adenine (EHNA) both inhibited I-125 - beta NGF retrograde transport. These results demonstrate that in vivo TrkA tyrosine kinase activity, actin filaments and dynein are involved in the retrograde transport of NGF. In addition, different PI3-kinase isoforms may be recruited within different neuronal populations to regulate the retrograde transport of NGF. Potentially, these isoforms could activate alternative signalling pathways, such as pp70S6K in sensory neurons. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:67 / 74
页数:8
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