Libby Richard T, Lillo Concepcion, Kitamoto Junko, Williams David S, Steel Karen P
MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK.
J Cell Sci. 2004 Sep 1;117(Pt 19):4509-15. doi: 10.1242/jcs.01316. Epub 2004 Aug 17.
Myosin Va is an actin-based motor molecule, one of a large family of unconventional myosins. In humans, mutations in MYO5A cause Griscelli syndrome type 1 and Elejalde syndrome, diseases characterized by pigmentation defects and the prepubescent onset of severe neurological deficits that ultimately lead to a shortened lifespan. Mutations in the Myo5a gene in mouse cause the dilute series of mouse mutants, demonstrating that myosin Va is involved in pigmentation and neural function. Although the reason for the pigmentation abnormalities is well understood, the role of myosin Va in neural function is not. Myosin Va has been found in synaptic terminals in the retina and brain. We report here new physiological evidence for a role of myosin Va in synaptic function. Photoreceptor synapses in neurologically affected myosin Va mutant mice have both anatomical and physiological abnormalities. Thus, myosin Va is required for normal photoreceptor signalling, suggesting that it might function in central nervous system synapses in general, with aberrant synaptic activity potentially underlying the neurological defects observed in dilute lethal mice and patients with Griscelli syndrome type 1 and Elejalde syndrome.
肌球蛋白Va是一种基于肌动蛋白的运动分子，是一大类非常规肌球蛋白中的一员。在人类中，MYO5A基因的突变会导致1型格里塞利综合征和埃雷亚尔德综合征，这些疾病的特征是色素沉着缺陷以及青春期前出现严重的神经功能缺损，最终导致寿命缩短。小鼠Myo5a基因的突变会导致一系列稀释小鼠突变体，表明肌球蛋白Va参与色素沉着和神经功能。尽管色素沉着异常的原因已得到充分理解，但肌球蛋白Va在神经功能中的作用尚不清楚。在视网膜和大脑的突触末端发现了肌球蛋白Va。我们在此报告肌球蛋白Va在突触功能中作用的新的生理学证据。神经功能受影响的肌球蛋白Va突变小鼠的光感受器突触存在解剖学和生理学异常。因此，正常的光感受器信号传导需要肌球蛋白Va，这表明它可能在整个中枢神经系统突触中发挥作用，异常的突触活动可能是稀释致死小鼠以及1型格里塞利综合征和埃雷亚尔德综合征患者中观察到的神经缺陷的潜在原因。
