Actin- and microtubule-dependent regulation of Golgi morphology by FHDC1.
Actin- and microtubule-dependent regulation of Golgi morphology by FHDC1.
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DOI：
10.1091/mbc.e15-02-0070
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发表时间：
2016-01-15
影响因子：
3.3
通讯作者：
Copeland JW
中科院分区：
文献类型：
--
作者：
Copeland SJ;Thurston SF;Copeland JW
肌动蛋白和微管骨架网络的协调作用是高尔基带组装所必需的。新的FHDC1聚集在高尔基体衍生的微管网络上，在那里它以肌动蛋白和微管依赖的方式调节高尔基体带组装。高尔基体是细胞内运输的中心枢纽，由顺式池、内侧池和反式池的束缚堆叠组成。在哺乳动物细胞中，这些池被缝合在一起，形成核周高尔基带，这是建立细胞极性和正常亚细胞组织所必需的。我们以前确定FHDC1（也称为INF 1）作为一个独特的微管结合的细胞壁重塑蛋白家族的成员。我们在这里表明，内源性FHDC1调节高尔基带的形成，并有一个明显的优先协会与高尔基体衍生的微管网络。敲低FHDC1表达导致高尔基体组装缺陷，并表明FHDC1在维持高尔基体衍生的微管网络中的作用。类似地，FHDC1的过表达诱导高尔基带分散成功能性微堆叠。这种效应不依赖于中心体衍生的微管，而是可能需要FHDC1微管结合结构域和高尔基体衍生的微管网络之间的相互作用。这些作用也依赖于FHDC1 FH2结构域和肌动蛋白细胞骨架之间的相互作用。因此，我们的研究结果表明，肌动蛋白和微管动力学的FHDC1的协调是正常的高尔基带形成所必需的。
The coordinated action of the actin and microtubule cytoskeletal networks is required for Golgi ribbon assembly. The novel formin FHDC1 accumulates on the Golgi-derived microtubule network, where it acts to regulate Golgi ribbon assembly in an actin- and microtubule-dependent manner. The Golgi apparatus is the central hub of intracellular trafficking and consists of tethered stacks of cis, medial, and trans cisternae. In mammalian cells, these cisternae are stitched together as a perinuclear Golgi ribbon, which is required for the establishment of cell polarity and normal subcellular organization. We previously identified FHDC1 (also known as INF1) as a unique microtubule-binding member of the formin family of cytoskeletal-remodeling proteins. We show here that endogenous FHDC1 regulates Golgi ribbon formation and has an apparent preferential association with the Golgi-derived microtubule network. Knockdown of FHDC1 expression results in defective Golgi assembly and suggests a role for FHDC1 in maintenance of the Golgi-derived microtubule network. Similarly, overexpression of FHDC1 induces dispersion of the Golgi ribbon into functional ministacks. This effect is independent of centrosome-derived microtubules and instead likely requires the interaction between the FHDC1 microtubule-binding domain and the Golgi-derived microtubule network. These effects also depend on the interaction between the FHDC1 FH2 domain and the actin cytoskeleton. Thus our results suggest that the coordination of actin and microtubule dynamics by FHDC1 is required for normal Golgi ribbon formation.