Ozsarac Nesrin, Weible Michael, Reynolds Anna J, Hendry Ian A
Developmental Neurobiology Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
J Neurosci Res. 2003 Apr 15;72(2):203-10. doi: 10.1002/jnr.10568.
Retrograde axonal transport of neurotrophins from nerve terminal to cell body requires a number of key processes, including internalization of the receptor-neurotrophin complex into vesicles and formation of multivesicular bodies and their transport along the axon. Previous studies have shown that each of these processes can be regulated by kinases. In this study, we looked at the role of protein kinase C (PKC) in retrograde transport by injecting labeled neurotrophins together with relevant pharmacological agents into the eye and measuring the accumulation of radioactivity in the trigeminal and superior cervical ganglia. Inhibitors of PKC, Ro-31-8220 and rottlerin, did not affect the retrograde transport of nerve growth factor (NGF); however, phorbol ester activation of classical and novel PKCs blocked retrograde transport. The effect of phorbol esters was partially reversed by rottlerin and Ro-31-8220. Activation of PKC has been shown to be involved in the disorganization of actin filaments. In this study, we show that Ro-31-8220 reverses growth cone collapse by phorbol 12-myristate 13-acetate and suggest that one of the effects of activating PKC on retrograde transport is to disrupt the actin filaments.
神经营养因子从神经末梢向细胞体的逆行轴突运输需要多个关键过程，包括受体 - 神经营养因子复合物内化到囊泡中、多泡体的形成及其沿轴突的运输。先前的研究表明，这些过程中的每一个都可受激酶调节。在本研究中，我们通过将标记的神经营养因子与相关药理试剂注入眼中，并测量三叉神经节和颈上神经节中放射性的积累，来研究蛋白激酶C（PKC）在逆行运输中的作用。PKC抑制剂Ro - 31 - 8220和rottlerin不影响神经生长因子（NGF）的逆行运输；然而，佛波酯对经典和新型PKC的激活却阻断了逆行运输。rottlerin和Ro - 31 - 8220可部分逆转佛波酯的作用。已证明PKC的激活与肌动蛋白丝的紊乱有关。在本研究中，我们表明Ro - 31 - 8220可逆转佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯引起的生长锥塌陷，并提示激活PKC对逆行运输的作用之一是破坏肌动蛋白丝。
