McGuire C B, Snipes G J, Norden J J
Department of Cell Biology, Vanderbilt University Medical School, Nashville, TN 37232.
Brain Res. 1988 Jun 1;469(1-2):277-91. doi: 10.1016/0165-3806(88)90189-7.
Growth-associated protein-43 (GAP-43) is a developmentally regulated, fast-axonally transported phosphoprotein whose synthesis and transport are enhanced during periods of growth and synaptic terminal formation. GAP-43 is a substrate of protein kinase C and is identical to protein F1, a phosphoprotein which is regulated during long-term potentiation in the hippocampus. In order to characterize the cellular localization of GAP-43, we have raised a specific antiserum against it, and used this as a probe to show that GAP-43 is neuron-specific, and is localized to growing neuronal processes in developing rat brain, and to presynaptic terminals in both the peripheral and central nervous system. In the mature CNS, GAP-43 immunoreactivity is present in most neuropil areas, but is especially dense in the molecular layers of the cerebellum, neocortex, and the hippocampus, structures known to exhibit synaptic plasticity. Its localization, together with biochemical data concerning the dynamics of its synthesis and its identity as protein F1, suggest that GAP-43 may be involved in axon growth in the developing nervous system, and in some aspect of synaptic plasticity in the mature CNS. These data also suggest that axon growth and synaptic plasticity in the brain may be regulated by a common mechanism, both involving the protein kinase C-mediated phosphorylation of GAP-43.
生长相关蛋白43(GAP - 43)是一种受发育调控的、快速轴突运输的磷蛋白,其合成和运输在生长及突触终末形成期间会增强。GAP - 43是蛋白激酶C的底物,与蛋白F1相同,蛋白F1是一种在海马体长期增强过程中受到调控的磷蛋白。为了描述GAP - 43的细胞定位,我们制备了针对它的特异性抗血清,并将其用作探针,以表明GAP - 43具有神经元特异性,定位于发育中大鼠脑内正在生长的神经元突起,以及外周和中枢神经系统的突触前终末。在成熟的中枢神经系统中,GAP - 43免疫反应性存在于大多数神经毡区域,但在小脑、新皮质和海马体的分子层中尤其密集,这些结构已知具有突触可塑性。其定位,连同关于其合成动态及作为蛋白F1身份的生化数据,表明GAP - 43可能参与发育中神经系统的轴突生长以及成熟中枢神经系统突触可塑性的某些方面。这些数据还表明,大脑中的轴突生长和突触可塑性可能受共同机制调控,两者均涉及蛋白激酶C介导的GAP - 43磷酸化。