Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin.
Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin.
复制标题
编织颗粒神经元被钙通道拮抗剂和针对层粘连蛋白B2链神经突生长结构域的抗体挽救。
DOI：
10.1083/jcb.134.2.477
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发表时间：
1996-07
影响因子：
7.8
通讯作者：
Wright, JM
中科院分区：
文献类型：
--
作者：
Liesi, P;Wright, JM
Weaver 突变会损害小脑颗粒神经元的迁移，并在出生后的前两周诱导神经元死亡。为了阐明神经元迁移受损的分子机制，我们在体外研究了编织者（wv/wv）颗粒神经元的拯救机制。我们发现，针对层粘连蛋白 B2 链的神经突生长结构域的抗体的 Fab2 片段增强了层粘连蛋白基质和已建立的电缆培养系统中织布颗粒神经元的神经突生长和神经元迁移。抗层粘连蛋白 B2 链的抗体对织布颗粒神经元的拯救可能是由于这些抗体对织布大脑中升高的 B2 链水平的中和作用。 L 型钙通道阻滞剂维拉帕米（1-5 µM）也拯救了织布颗粒神经元。高浓度的MK-801（10-20μM），一种谷氨酸受体拮抗剂和电压门控钙通道阻滞剂，与维拉帕米类似，可以拯救织布颗粒神经元，但低浓度的MK-801（1μM）没有拯救作用。同时进行的膜片钳研究表明，织布颗粒神经元不表达功能性 N-甲基-D-天冬氨酸受体，进一步表明 MK-801 对织布颗粒神经元的拯救是由于其已知的电压门控钙通道抑制作用。目前的结果表明，针对层粘连蛋白 B2 链、维拉帕米和高浓度 MK-801 的抗体可以保护织布颗粒神经元免受织布基因的其他破坏性作用。因此，层粘连蛋白系统和钙通道功能均导致织布颗粒神经元的迁移缺陷。
The weaver mutation impairs migration of the cerebellar granular neurons and induces neuronal death during the first two weeks of postnatal life. To elucidate the molecular mechanisms for the impaired neuronal migration, we investigated the rescue mechanisms of the weaver (wv/wv) granule neurons in vitro. We found that Fab2 fragments of antibodies against a neurite outgrowth domain of the B2 chain of laminin enhanced neurite outgrowth and neuronal migration of the weaver granule neurons on a laminin substratum and in the established cable culture system. The rescue of the weaver granule neurons by antibodies against the B2 chain of laminin may result from the neutralizing effect of these antibodies against the elevated B2 chain levels of the weaver brain. The L-type calcium channel blocker, verapamil (1-5 microM), also rescued the weaver granule neurons. High concentrations of MK-801 (10- 20 microM), a glutamate receptor antagonist and voltage-gated calcium channel blocker, rescued the weaver granule neurons similar to verapamil, but low concentrations of MK-801 (1 microM) had no rescue effect. Simultaneous patch-clamp studies indicated that the weaver granule neurons did not express functional N-methyl-D-aspartate receptors further indicating that the rescue of the weaver granule neurons by MK-801 resulted from its known inhibition of voltage-gated calcium channels. The present results indicate that antibodies against the B2 chain of laminin, verapamil, and high concentrations of MK-801 protect the weaver granule neurons from the otherwise destructive action of the weaver gene. Thus, both the laminin system and calcium channel function contribute to the migration deficiency of the weaver granule neurons.
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影响因子：
5.5
作者：
FFRENCHMULLEN, JMH;ROGAWSKI, MA
通讯作者：
ROGAWSKI, MA
影响因子：
30.8
作者：
PATIL, N;COX, DR;PETERSON, AS
通讯作者：
PETERSON, AS
DOI：
10.1073/pnas.70.1.240
发表时间：
1973-01-01
影响因子：
11.1
作者：
RAKIC, P;SIDMAN, RL
通讯作者：
SIDMAN, RL
影响因子：
4.2
作者：
HAGER, G;DODT, HU;LIESI, P
通讯作者：
LIESI, P
影响因子：
64.8
作者：
FARRANT, M;FELDMEYER, D;CULLCANDY, SG
通讯作者：
CULLCANDY, SG