A potential role for shed soluble major histocompatibility class I molecules as modulators of neurite outgrowth.
A potential role for shed soluble major histocompatibility class I molecules as modulators of neurite outgrowth.
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DOI：
10.1371/journal.pone.0018439
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发表时间：
2011-03-31
期刊：
影响因子：
3.7
通讯作者：
Kaufman DL
中科院分区：
文献类型：
--
作者：
Washburn LR;Zekzer D;Eitan S;Lu Y;Dang H;Middleton B;Evans CJ;Tian J;Kaufman DL
经典主要组织相容性 I 类 (MHCI) 分子的神经生物学活性刚刚开始被探索。为了进一步检查 MHCI 在神经元连接形成过程中的作用，我们在距野生型丘脑外植体或来自转基因小鼠（称为“NSE-Db”）的丘脑（其神经元表达更高水平的 MHCI）的丘脑附近培养了胚胎小鼠视网膜外植体。虽然视网膜神经突延伸与野生型丘脑形成连接，但我们惊讶地发现，在 NSE-Db 丘脑外植体附近的区域，视网膜神经突的生长非常受阻，这表明来自这些丘脑的扩散因子抑制了视网膜神经突的生长。人们早就知道，由于完整 MHCI 分子的脱落，以及其重链的选择性外显子剪接或裂解其跨膜锚的作用蛋白酶，表达 MHCI 的细胞会释放可溶形式的 MHCI (sMHCI)。我们发现来自 NSE-Db 丘脑的扩散抑制因子是 sMHCI。我们还表明，被编程为表达小鼠 MHCI 的 COS 细胞会释放 sMHCI，从而在体外抑制附近神经元的轴突生长。 sMHCI 的神经抑制作用可以通过降低 cAMP 水平来阻断，这表明神经元 MHCI 受体的信号传导机制涉及环核苷酸依赖性途径。我们的结果表明，MHCI 不仅以其膜结合形式具有神经生物学活性，还可能作为可溶性分子影响局部神经元。我们讨论补体蛋白在生成 sMHCI 中的参与以及 MHCI 在神经系统中生物活性的新理论模型。
The neurobiological activities of classical major histocompatibility class I (MHCI) molecules are just beginning to be explored. To further examine MHCI's actions during the formation of neuronal connections, we cultured embryonic mouse retina explants a short distance from wildtype thalamic explants, or thalami from transgenic mice (termed “NSE-Db”) whose neurons express higher levels of MHCI. While retina neurites extended to form connections with wildtype thalami, we were surprised to find that retina neurite outgrowth was very stunted in regions proximal to NSE-Db thalamic explants, suggesting that a diffusible factor from these thalami inhibited retina neurite outgrowth. It has been long known that MHCI-expressing cells release soluble forms of MHCI (sMHCI) due to the shedding of intact MHCI molecules, as well as the alternative exon splicing of its heavy chain or the action proteases which cleave off it's transmembrane anchor. We show that the diffusible inhibitory factor from the NSE-Db thalami is sMHCI. We also show that COS cells programmed to express murine MHCI release sMHCI that inhibits neurite outgrowth from nearby neurons in vitro. The neuroinhibitory effect of sMHCI could be blocked by lowering cAMP levels, suggesting that the neuronal MHCI receptor's signaling mechanism involves a cyclic nucleotide-dependent pathway. Our results suggest that MHCI may not only have neurobiological activity in its membrane-bound form, it may also influence local neurons as a soluble molecule. We discuss the involvement of complement proteins in generating sMHCI and new theoretical models of MHCI's biological activities in the nervous system.
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DOI：
10.4049/jimmunol.0902159
发表时间：
2010-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Escande-Beillard N;Washburn L;Zekzer D;Wu ZP;Eitan S;Ivkovic S;Lu Y;Dang H;Middleton B;Bilousova TV;Yoshimura Y;Evans CJ;Joyce S;Tian J;Kaufman DL
通讯作者：
Kaufman DL
影响因子：
56.9
作者：
Huh, GS;Boulanger, LM;Shatz, CJ
通讯作者：
Shatz, CJ
DOI：
10.1016/0167-4838(90)90169-g
发表时间：
1990-02-09
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ERIKSSON, H;NISSEN, MH
通讯作者：
NISSEN, MH
DOI：
10.1084/jem.163.5.1173
发表时间：
1986-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Krangel MS
通讯作者：
Krangel MS
影响因子：
5.4
作者：
Kimura, T;Griffin, DE
通讯作者：
Griffin, DE