The zebrafish nrc mutant reveals a role for the polyphosphoinositide phosphatase synaptojanin 1 in cone photoreceptor ribbon anchoring
The zebrafish nrc mutant reveals a role for the polyphosphoinositide phosphatase synaptojanin 1 in cone photoreceptor ribbon anchoring
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DOI：
10.1523/jneurosci.2892-04.2004
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发表时间：
2004-10-06
影响因子：
5.3
通讯作者：
Brockerhoff, SE
中科院分区：
文献类型：
--
作者：
Van Epps, HA;Hayashi, M;Brockerhoff, SE
视觉、前庭和听觉神经元依靠带状突触来快速、持续地释放和回收突触小泡。负责带状突触特性的分子机制大多是未知的。斑马鱼视觉突变体NRC在锥状光感受器突触具有非锚定的条带和异常的突触传递。我们使用定位克隆来确定NRC突变是synaptojanin1(Synj1)基因中的一个过早终止密码子。突触素1(Synaptojanin 1，Synj1)在NRC提取物中检测不到，与其相关的生化活性降低。此外，针对synj1表型的吗啉类化合物可复制NRC突变。Synj1是一种多聚磷脂酰肌醇磷酸酶，在传统的突触中起重要作用，参与网状蛋白介导的内吞作用和肌动蛋白细胞骨架重排。在NRC锥形感光细胞椎弓根中，不仅突触带未被锚定，而且突触小泡数量减少，分布不规则，散布在致密的细胞骨架基质中。我们的发现揭示了Synj1的新作用，并将磷脂酰肌醇代谢与锥状光感受器突触的带状结构和功能联系起来。
Visual, vestibular, and auditory neurons rely on ribbon synapses for rapid continuous release and recycling of synaptic vesicles. Molecular mechanisms responsible for the properties of ribbon synapses are mostly unknown. The zebrafish vision mutant nrc has unanchored ribbons and abnormal synaptic transmission at cone photoreceptor synapses. We used positional cloning to identify the nrc mutation as a premature stop codon in the synaptojanin1 (synj1) gene. Synaptojanin 1 (Synj1) is undetectable in nrc extracts, and biochemical activities associated with it are reduced. Furthermore, morpholinos directed against synj1 phenocopy the nrc mutation. Synj1 is a polyphosphoinositide phosphatase important at conventional synapses for clathrin-mediated endocytosis and actin cytoskeletal rearrangement. In the nrc cone photoreceptor pedicle, not only are ribbons unanchored, but synaptic vesicles are reduced in number, abnormally distributed, and interspersed within a dense cytoskeletal matrix. Our findings reveal a new role for Synj1 and link phosphoinositide metabolism to ribbon architecture and function at the cone photoreceptor synapse.