Scyl1 regulates Golgi morphology.
Scyl1 regulates Golgi morphology.
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DOI：
10.1371/journal.pone.0009537
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发表时间：
2010-03-04
期刊：
影响因子：
3.7
通讯作者：
McPherson PS
中科院分区：
文献类型：
--
作者：
Burman JL;Hamlin JN;McPherson PS
膜运输是真核细胞的一个决定性特征，对于维持细胞器稳态和特性至关重要。我们之前发现 Scy1 样 1 (Scyl1) 是催化失活蛋白激酶 Scy1 样家族的成员，是 COPI 涂层的高亲和力结合伴侣。 COPI 包被的囊泡控制高尔基体到内质网的运输，我们观察到 Scyl1 功能的破坏导致 KDEL 受体通过 COPI 途径的运输减少。我们推断，如果 Scyl1 在 COPI 运输中发挥重要作用，那么它的破坏可能会影响高尔基体稳态。我们使用先前建立的方法在培养细胞中进行 Scyl1 敲除，并观察到高尔基体形态的变化。 Scyl1 耗尽的细胞中高尔基体的表面积和体积均增加，但细胞器的连续性和极性未受影响。在超微结构水平上，我们观察到高尔基体的有序结构随着池腔宽度的增加而减少，而高尔基体池的数量保持不变。高尔金蛋白家族形成了控制高尔基体稳态的抗去污剂网络。通过敲除高尔金 p115 来破坏该蛋白质网络会破坏 Scyl1 的高尔基体定位。此外，我们发现 Scyl1 与 58K/formiminotransferase cyclodeaminase (FTCD) 相互作用，FTCD 是一种与高尔基体顺面紧密相关的蛋白质。我们的结果将 Scyl1 置于高尔金网络和 COPI 运输之间的界面，并证明 Scyl1 是维持高尔基体形态所必需的。结合其他人的观察结果，即 Scyl1 是导致神经退行性小鼠模型 mdf 的基因产物，我们的结果还暗示了神经退行性变中 COPI 运输和高尔基体稳态的调节。
Membrane trafficking is a defining feature of eukaryotic cells, and is essential for the maintenance of organelle homeostasis and identity. We previously identified Scy1-like 1 (Scyl1), a member of the Scy1-like family of catalytically inactive protein kinases, as a high-affinity binding partner of COPI coats. COPI-coated vesicles control Golgi to endoplasmic reticulum trafficking and we observed that disruption of Scyl1 function leads to a decrease in trafficking of the KDEL receptor via the COPI pathway. We reasoned that if Scyl1 plays a major role in COPI trafficking its disruption could influence Golgi homeostasis. We performed Scyl1 knock down in cultured cells using previously established methods and observed an alteration in Golgi morphology. Both the surface area and volume of the Golgi is increased in Scyl1-depleted cells, but the continuity and polarity of the organelle is unperturbed. At the ultrastructural level we observe a decrease in the orderly structure of the Golgi with an increase in cisternal luminal width, while the number of Golgi cisternae remains unchanged. The golgin family of proteins forms a detergent resistant network that controls Golgi homeostasis. Disruption of this protein network by knock down of the golgin p115 disrupts the Golgi localization of Scyl1. Moreover, we find that Scyl1 interacts with 58K/formiminotransferase cyclodeaminase (FTCD), a protein that is tightly associated with the cis face of the Golgi. Our results place Scyl1 at an interface between the golgin network and COPI trafficking and demonstrate that Scyl1 is required for the maintenance of Golgi morphology. Coupled with the observation from others that Scyl1 is the gene product responsible for the neurodegenerative mouse model mdf, our results additionally implicate the regulation of COPI trafficking and Golgi homeostasis in neurodegeneration.
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