Hoffman P N
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Neurosci. 1989 Mar;9(3):893-7. doi: 10.1523/JNEUROSCI.09-03-00893.1989.
GAP-43 is a membrane-associated phosphoprotein enriched in elongating axons (Meiri et al., 1986; Skene et al., 1986). After an axon has been interrupted by cutting or crushing a nerve (axotomy), the portion of the axon disconnected from the cell body (distal stump) degenerates and is replaced by the outgrowth (elongation) of regenerating sprouts arising from the proximal stump. Previous studies have shown that increased amounts of pulse-labeled GAP-43 undergo fast axonal transport in regenerating neurons (Benowitz et al., 1981; Skene and Willard, 1981 a, b). Using hybridization with a cloned cDNA probe, I now show that mRNA levels for GAP-43 increase in lumbar sensory neurons of rat after regeneration is initiated by crushing the sciatic nerve; the relatively high levels of GAP-43 mRNA in regenerating neurons are comparable to those in the developing neurons of 5-d-old animals. I further demonstrate that the induction of GAP-43 expression in regenerating neurons coincides temporally with an increase in mRNA levels for class II beta tubulin (Hoffman and Cleveland, 1988), suggesting that the expression of these proteins is closely coordinated during axonal elongation.
生长相关蛋白-43(GAP-43)是一种与膜相关的磷蛋白,在伸长的轴突中含量丰富(梅里等人,1986年;斯凯纳等人,1986年)。在轴突因切断或挤压神经(轴突切断术)而中断后,与细胞体断开连接的轴突部分(远端残端)会退化,并被近端残端产生的再生芽的生长(伸长)所取代。先前的研究表明,在再生神经元中,大量脉冲标记的GAP-43会进行快速轴突运输(贝诺维茨等人,1981年;斯凯纳和威拉德,1981年a、b)。通过与克隆的cDNA探针杂交,我现在表明,在挤压坐骨神经引发再生后,大鼠腰段感觉神经元中GAP-43的mRNA水平会升高;再生神经元中相对较高水平的GAP-43 mRNA与5日龄动物发育中的神经元中的水平相当。我进一步证明,再生神经元中GAP-43表达的诱导在时间上与II类β微管蛋白的mRNA水平增加相吻合(霍夫曼和克利夫兰,1988年),这表明这些蛋白质的表达在轴突伸长过程中密切协调。