Classical 18.5-and 21.5-kDa isoforms of myelin basic protein inhibit calcium influx into oligodendroglial cells, in contrast to golli isoforms.
Classical 18.5-and 21.5-kDa isoforms of myelin basic protein inhibit calcium influx into oligodendroglial cells, in contrast to golli isoforms.
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与GOLLI同工型相反，经典的18.5和21.5-kDa同工型抑制钙的流入少突胶质细胞。
DOI：
10.1002/jnr.22570
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发表时间：
2011-04
影响因子：
4.2
通讯作者：
Harauzi, George
中科院分区：
文献类型：
--
作者：
Smith, Graham S. T.;Paez, Pablo M.;Spreuer, Vilma;Campagnoni, Celia W.;Boggs, Joan M.;Campagnoni, Anthony T.;Harauzi, George
关键词：
髓鞘碱性蛋白（MBP）家族起源于golli（少突胶质细胞谱系基因）复合体的不同转录起始位点，通过差异剪接产生进一步的多样性。“经典的”MBP同种型是促进成熟髓鞘的致密化但也具有多种蛋白质相互作用的外周膜蛋白。早期发育的golli亚型先前已被证明可以促进过程延伸，并增强Ca 2+流入原代和永生化少突胶质细胞系。在这里，我们进行了类似的研究与经典的18.5和21.5 kDa的MBP亚型。与golli蛋白相反，经典MBP亚型的过表达显著降低了少突胶质细胞系N19以及少突胶质祖细胞原代培养物中的Ca 2+内流。药理学实验表明，这种作用是由电压操纵的Ca 2+通道（VOCC）介导的，而不是由配体门控的Ca 2+通道或从细胞内储存的Ca 2+释放。假脱亚胺化的18.5-kDa和全长21.5-kDa同种型不像未修饰的18.5-kDa同种型那样减少Ca 2+内流。然而，更有效的膜定位（包含21-nt 3′-非翻译区转运信号的经典MBP的过表达、假脱亚氨基的18.5-kDa和21.5-kDa亚型）进一步降低了质膜去极化后的Ca 2+反应，表明经典MBP亚型与质膜的结合对于调节Ca 2+稳态很重要。此外，我们已经发现，成熟的18.5 kDa亚型表达少突胶质细胞与VOCCs共定位，特别是在延伸膜过程的前沿。总之，我们的研究结果表明，经典的MBP蛋白在调节电压门控钙通道在少突胶质细胞的质膜，从而也在调节多个发育阶段，在这个细胞系的关键作用。
The myelin basic protein (MBP) family arises from different transcription start sites of the golli (gene of oligodendrocyte lineage) complex, with further variety generated by differential splicing. The “classical” MBP isoforms are peripheral membrane proteins that facilitate compaction of the mature myelin sheath but also have multiple protein interactions. The early developmental golli isoforms have previously been shown to promote process extension and enhance Ca2+ influx into primary and immortalized oligodendrocyte cell lines. Here, we have performed similar studies with the classical 18.5- and 21.5-kDa isoforms of MBP. In contrast to golli proteins, overexpression of classical MBP isoforms significantly reduces Ca2+ influx in the oligodendrocyte cell line N19 as well as in primary cultures of oligodendroglial progenitor cells. Pharmacological experiments demonstrate that this effect is mediated by voltage-operated Ca2+ channels (VOCCs) and not by ligand-gated Ca2+ channels or Ca2+ release from intracellular stores. The pseudo-deiminated 18.5-kDa and the full-length 21.5-kDa isoforms do not reduce Ca2+ influx as much as the unmodified 18.5-kDa isoform. However, more efficient membrane localization (of overexpressed, pseudo-deiminated 18.5-kDa and 21.5-kDa isoforms of classical MBP containing the 21-nt 3′-untranslated region transit signal) further reduces the Ca2+ response after plasma membrane depolarization, suggesting that binding of classical MBP isoforms to the plasma membrane is important for modulation of Ca2+ homeostasis. Furthermore, we have found that the mature 18.5-kDa isoform expressed in oligodendrocytes colocalizes with VOCCs, particularly at the leading edge of extending membrane processes. In summary, our findings suggest a key role for classical MBP proteins in regulating voltage-gated Ca2+ channels at the plasma membrane of oligodendroglial cells and thus also in regulation of multiple developmental stages in this cell lineage.
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影响因子：
4.7
作者：
Fulton D;Paez PM;Campagnoni AT
通讯作者：
Campagnoni AT
影响因子：
64.8
作者：
Bergles, DE;Roberts, JDB;Jahr, CE
通讯作者：
Jahr, CE
影响因子：
3.4
作者：
Agresti, C;DUrso, D;Levi, G
通讯作者：
Levi, G
DOI：
10.1073/pnas.91.19.8812
发表时间：
1994-09-13
影响因子：
11.1
作者：
BYRAVAN, S;FOSTER, LM;CAMPAGNONI, AT
通讯作者：
CAMPAGNONI, AT
影响因子：
2.9
作者：
FOSTER, LM;LANDRY, C;CAMPAGNONI, AT
通讯作者：
CAMPAGNONI, AT