Proliferative arrest of neural cells induces prion protein synthesis, nanotube formation, and cell-to-cell contacts.
Proliferative arrest of neural cells induces prion protein synthesis, nanotube formation, and cell-to-cell contacts.
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DOI：
10.1002/jcb.22723
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Manuelidis, Laura
中科院分区：
文献类型：
--
作者：
Miyazawa, Kohtaro;Emmerling, Kaitlin;Manuelidis, Laura
关键词：
宿主蛋白(PrP)在神经元中含量最丰富，其功能尚不清楚。PRP mRNA转录产物在与细胞分裂停滞和终末分化相关的关键发育时期积累。我们试图找出增殖停滞是否足以导致发育中神经元PrP的增加。在终末分化前用温度敏感的SV40T抗原转导的大鼠神经元前体细胞(在33℃下允许，但在37.5℃下不允许)进行了分析。37.5℃培养2天后，所有细胞的T抗原均降低，仅有少量DNA合成(BrdU+)细胞。37.5℃诱导的增殖停滞使PrP增加4倍。当与降低的血清相结合时，发现增加了7倍。在2天内，额外的突起和丰富的质膜PrP连接了许多细胞。PRP也集中在相对的静止细胞之间，以及延伸的生长锥和它们的丝状基座上。固定细胞在原板中保持30天，并在33°C恢复到低PrP增殖状态。超微结构研究证实，纳米管增加和高PrP细胞之间的粘连连接。此外，一些细胞共享细胞质，这些明显开放的区域可能是在活细胞中观察到的细胞器和病毒交换的管道。因此，PrP与动态识别和接触功能有关，并可能参与胚胎发育关键时刻神经合胞的瞬时形成。该系统可以用来识别抑制传染性CJD颗粒通过神经系统运输和传播的药物。
Host prion protein (PrP) is most abundant in neurons where its functions are unclear. PrP mRNA transcripts accumulate at key developmental times linked to cell division arrest and terminal differentiation. We sought to find if proliferative arrest was sufficient to cause an increase in PrP in developing neurons. Rat neuronal precursor cells transduced with the temperature sensitive SV40 T antigen just before terminal differentiation (permissive at 33°C but not at 37.5°C) were analyzed. By 2 days, T antigen was decreased in all cells at 37.5°C, with few DNA synthesizing (BrdU+) cells. Proliferative arrest induced by 37.5°C yielded a 4-fold PrP increase. When combined with reduced serum, a 7-fold increase was found. Within 2 days additional neuritic processes with abundant plasma membrane PrP connected many cells. PrP also concentrated between apposed stationary cells, and on extending growth cones and their filopodia. Stationary cells were maintained for 30 days in their original plate, and they reverted to a proliferating low PrP state at 33°C. Ultrastructural studies confirmed increased nanotubes and adherent junctions between high PrP cells. Additionally, some cells shared cytoplasm and these apparently open regions are likely conduits for the exchange of organelles and viruses that have been observed in living cells. Thus PrP is associated with dynamic recognition and contact functions, and may be involved in the transient formation of neural syncytia at key times in embryogenesis. This system can be used to identify drugs that inhibit the transport and spread of infectious CJD particles through the nervous system.
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影响因子：
158.5
作者：
MANUELIDIS, EE;ANGELO, JN;MANUELIDIS, L
通讯作者：
MANUELIDIS, L
影响因子：
12.7
作者：
MANUELIDIS, L;MANUELIDIS, EE
通讯作者：
MANUELIDIS, EE
影响因子：
11.4
作者：
Leblanc, Pascal;Alais, Sandrine;Darlix, Jean Luc
通讯作者：
Darlix, Jean Luc
影响因子：
0.6
作者：
KAY, LE
通讯作者：
KAY, LE
DOI：
10.1073/pnas.0400158101
发表时间：
2004-06-08
影响因子：
11.1
作者：
Arjona, A;Simarro, L;Manuelidis, L
通讯作者：
Manuelidis, L