Su Yuhua, Balice-Gordon Rita J, Hess Darren M, Landsman Douglas S, Minarcik Jeremy, Golden Jeffrey, Hurwitz Ivy, Liebhaber Stephen A, Cooke Nancy E
Department of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Neurosci. 2004 Apr 7;24(14):3627-36. doi: 10.1523/JNEUROSCI.4644-03.2004.
We report a random disruption in the mouse genome that resulted in lethal paralysis in homozygous newborns. The disruption blocked expression of neurobeachin, a protein containing a BEACH (beige and Chediak-Higashi) domain implicated in synaptic vesicle trafficking and an AKAP (A-kinase anchor protein) domain linked to localization of cAMP-dependent protein kinase activity. nbea-null mice demonstrated a complete block of evoked synaptic transmission at neuromuscular junctions, whereas nerve conduction, synaptic structure, and spontaneous synaptic vesicle release were completely normal. These findings support an essential role for neurobeachin in evoked neurotransmitter release at neuromuscular junctions and suggest that it plays an important role in synaptic transmission.
我们报道了小鼠基因组中的一个随机破坏事件，该事件导致纯合新生小鼠出现致命性麻痹。这种破坏阻断了神经beachin的表达，神经beachin是一种蛋白质，包含一个与突触小泡运输有关的BEACH（米色和切迪阿克-东希）结构域以及一个与环磷酸腺苷依赖性蛋白激酶活性定位相关的AKAP（A激酶锚定蛋白）结构域。nbea基因敲除小鼠在神经肌肉接头处表现出诱发突触传递的完全阻断，而神经传导、突触结构和自发突触小泡释放则完全正常。这些发现支持了神经beachin在神经肌肉接头处诱发神经递质释放中起关键作用，并表明它在突触传递中发挥重要作用。
