Krejci E, Gasnier B, Botton D, Isambert M F, Sagné C, Gagnon J, Massoulié J, Henry J P
Laboratoire de Neurobiologie, CNRS Unité Associée 295, Ecole Normale Supérieure, Paris, France.
FEBS Lett. 1993 Nov 29;335(1):27-32. doi: 10.1016/0014-5793(93)80432-t.
In monoaminergic cells, the neurotransmitter is accumulated into secretory or synaptic vesicles by a tetrabenazine- and reserpine-sensitive transporter, catalyzing an H+/monoamine antiport. The major vesicular monoamine transporter from bovine chromaffin cells was cloned, using sequences common to adrenal medulla and brain rat vesicular monoamine transporters. Its identity was confirmed by peptide sequences, determined from the purified protein. Surprisingly, the bovine adrenal medulla sequence, bVMAT2, is more related to the transporter from human and rat brain than to that from rat adrenal medulla. PCR amplification showed that bVMAT2 is expressed in both adrenal medulla and brain, in contrast with the situation reported in rats, where distinct genes appear to be expressed in brain (SVAT or MAT, now renamed rVMAT2) and in the adrenal medulla (CGAT, now renamed rVMAT1). In bovine chromaffin cells, long-term depolarization by KCl resulted in an increase in the level of bVMAT2 mRNA, in agreement with the previously observed increase in the transporter binding sites, suggesting that a coupling between stimulation, secretion and synthesis changes the composition of the secretory granule membrane.
在单胺能细胞中,神经递质通过一种对丁苯那嗪和利血平敏感的转运体积累到分泌性或突触小泡中,该转运体催化H⁺/单胺反向转运。利用肾上腺髓质和大鼠脑囊泡单胺转运体的共同序列,克隆了来自牛嗜铬细胞的主要囊泡单胺转运体。通过从纯化蛋白中测定的肽序列证实了其身份。令人惊讶的是,牛肾上腺髓质序列bVMAT2与人类和大鼠脑内的转运体的关系比与大鼠肾上腺髓质转运体的关系更为密切。PCR扩增显示bVMAT2在肾上腺髓质和脑中均有表达,这与大鼠的情况相反,在大鼠中,不同的基因似乎分别在脑(SVAT或MAT,现重新命名为rVMAT2)和肾上腺髓质(CGAT,现重新命名为rVMAT1)中表达。在牛嗜铬细胞中,KCl引起的长期去极化导致bVMAT2 mRNA水平升高,这与之前观察到的转运体结合位点增加一致,表明刺激、分泌和合成之间的偶联改变了分泌颗粒膜的组成。