Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA.
J Neurosci Res. 2010 Dec;88(16):3447-56. doi: 10.1002/jnr.22513. Epub 2010 Oct 8.
Scaffolding proteins play a critical role in the proper development and function of neural circuits. In contrast to the case for excitatory circuits, in which the role of several scaffolding proteins has been characterized, less is known about the scaffolding proteins that regulate inhibitory neurotransmission. The ankyrin repeat-rich membrane spanning (ARMS)/kinase D-interacting substrate of 220 kDa (Kidins220) scaffolding protein is expressed during the establishment of γ-aminobutyric acid (GABA) neurotransmission and is highly regulated by activity. To evaluate whether ARMS/Kidins220 expression affects GABAergic neurotransmission, we modified the ARMS/Kidins220 levels during the period of its maximum expression in culture (DIV 1-10). Whereas a decrease in ARMS/Kidins220 levels suppressed GABAergic neurotransmission, overexpression of ARMS/Kidins220 produced an increase in GABAergic neurotransmission in hippocampal neurons. In addition, we found that ARMS/Kidins220 regulates GABAergic neurotransmission by a presynaptic mechanism. Our results suggest that the ARMS/Kidins220 scaffold protein plays a critical role in the regulation of inhibitory transmission in hippocampal neurons.
支架蛋白在神经回路的正常发育和功能中起着关键作用。与兴奋性回路的情况不同，几种支架蛋白的作用已经得到了描述，而调节抑制性神经传递的支架蛋白则知之甚少。富含锚蛋白重复序列的跨膜（ARMS）/激酶 D 相互作用的 220 kDa 底物（Kidins220）支架蛋白在γ-氨基丁酸（GABA）神经传递的建立过程中表达，并高度受活性调节。为了评估 ARMS/Kidins220 的表达是否影响 GABA 能神经传递，我们在培养物中 ARMS/Kidins220 表达的最高时期（DIV 1-10）改变了 ARMS/Kidins220 的水平。虽然 ARMS/Kidins220 水平的降低抑制了 GABA 能神经传递，但 ARMS/Kidins220 的过表达导致海马神经元中 GABA 能神经传递增加。此外，我们发现 ARMS/Kidins220 通过突触前机制调节 GABA 能神经传递。我们的结果表明，ARMS/Kidins220 支架蛋白在调节海马神经元中的抑制性传递中起着关键作用。
