The Trypanosoma brucei subpellicular microtubule array is organized into functionally discrete subdomains defined by microtubule associated proteins.
The Trypanosoma brucei subpellicular microtubule array is organized into functionally discrete subdomains defined by microtubule associated proteins.
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DOI：
10.1371/journal.ppat.1009588
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发表时间：
2021-05
期刊：
影响因子：
6.7
通讯作者：
de Graffenried CL
中科院分区：
文献类型：
--
作者：
Sinclair AN;Huynh CT;Sladewski TE;Zuromski JL;Ruiz AE;de Graffenried CL
微管是固有的动态细胞骨架聚合物，其长度和组织可以改变以在真核细胞中执行基本功能，例如为细胞内运输提供轨道并形成有丝分裂纺锤体。微管可以被捆绑以产生更稳定的结构，共同传播力，例如在鞭毛轴丝中，它提供运动性。原生生物寄生虫布氏锥虫（Trypanosoma brucei）的膜下微管阵列是高度特化的微管束的一个显著例子，布氏锥虫是非洲昏睡病的病原体。它由单层微管组成，这些微管彼此交联并与上覆的质膜交联。阵列微管似乎是高度稳定的，并保持完整的整个细胞周期，但很少有人知道的途径，调整微管的特性锥虫。在这里，我们表明，薄膜下微管阵列被组织成子域，包括差异定位阵列相关蛋白在阵列后，中，前。阵列相关蛋白PAVE 1稳定细胞后部的阵列微管，并对维持其锥形形状至关重要。PAVE 1和新鉴定的蛋白质PAVE 2形成直接与微管晶格结合的复合物，表明它们是真正的动质体特异性MAP。TbAIR9定位于整个膜下阵列，对于维持阵列相关蛋白在其各自的阵列子域内的定位是必需的。阵列内蛋白质的排列可能会调整阵列微管的局部特性，并产生细胞的不对称形状，这对寄生虫的生存能力至关重要。许多寄生原生生物使用微管阵列接触质膜的内小叶，通常称为膜下微管阵列，以将其细胞塑造成允许其有效感染宿主的形式。虽然在广泛的寄生虫中发现了表膜下阵列，但对它们如何组装和维持知之甚少。布氏锥虫是人类非洲锥虫病的病原体，它有一个精心制作的膜下阵列，产生寄生虫的螺旋形状，这是它在拥挤和粘稠的溶液中移动的能力所必需的。我们已经确定了一系列在阵列中具有一系列定位模式的蛋白质，这表明阵列受到阵列相关蛋白质的亚结构域的调节，这些亚结构域可能调节微管的局部特性以适应细胞体不同部位的应力。这些结果建立了一个基础，了解锥虫subpellicular阵列是如何建立，形状和维护，这是以前没有考虑过的。
Microtubules are inherently dynamic cytoskeletal polymers whose length and organization can be altered to perform essential functions in eukaryotic cells, such as providing tracks for intracellular trafficking and forming the mitotic spindle. Microtubules can be bundled to create more stable structures that collectively propagate force, such as in the flagellar axoneme, which provides motility. The subpellicular microtubule array of the protist parasite Trypanosoma brucei, the causative agent of African sleeping sickness, is a remarkable example of a highly specialized microtubule bundle. It is comprised of a single layer of microtubules that are crosslinked to each other and to the overlying plasma membrane. The array microtubules appear to be highly stable and remain intact throughout the cell cycle, but very little is known about the pathways that tune microtubule properties in trypanosomatids. Here, we show that the subpellicular microtubule array is organized into subdomains that consist of differentially localized array-associated proteins at the array posterior, middle, and anterior. The array-associated protein PAVE1 stabilizes array microtubules at the cell posterior and is essential for maintaining its tapered shape. PAVE1 and the newly identified protein PAVE2 form a complex that binds directly to the microtubule lattice, demonstrating that they are a true kinetoplastid-specific MAP. TbAIR9, which localizes to the entirety of the subpellicular array, is necessary for maintaining the localization of array-associated proteins within their respective subdomains of the array. The arrangement of proteins within the array likely tunes the local properties of array microtubules and creates the asymmetric shape of the cell, which is essential for parasite viability. Many parasitic protists use arrays of microtubules that contact the inner leaflet of the plasma membrane, typically known as subpellicular microtubule arrays, to shape their cells into forms that allow them to efficiently infect their hosts. While subpellicular arrays are found in a wide range of parasites, very little is known about how they are assembled and maintained. Trypanosoma brucei, which is the causative agent of human African trypanosomiasis, has an elaborate subpellicular array that produces the helical shape of the parasite, which is essential for its ability to move within crowded and viscous solutions. We have identified a series of proteins that have a range of localization patterns within the array, which suggests that the array is regulated by subdomains of array-associated proteins that likely tune the local properties of the microtubules to suit the stresses found at different parts of the cell body. These results establish a foundation to understand how trypanosomatid subpellicular arrays are built, shaped, and maintained, which has not previously been considered.
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影响因子：
14.9
作者：
Blum M;Chang HY;Chuguransky S;Grego T;Kandasaamy S;Mitchell A;Nuka G;Paysan-Lafosse T;Qureshi M;Raj S;Richardson L;Salazar GA;Williams L;Bork P;Bridge A;Gough J;Haft DH;Letunic I;Marchler-Bauer A;Mi H;Natale DA;Necci M;Orengo CA;Pandurangan AP;Rivoire C;Sigrist CJA;Sillitoe I;Thanki N;Thomas PD;Tosatto SCE;Wu CH;Bateman A;Finn RD
通讯作者：
Finn RD
影响因子：
2.3
作者：
Griffiths, Gareth;Lucocq, John Milton
通讯作者：
Lucocq, John Milton
影响因子：
14.9
作者：
Buchan, Daniel W. A.;Jones, David T.
通讯作者：
Jones, David T.
DOI：
10.1073/pnas.84.10.3259
发表时间：
1987-05-01
影响因子：
11.1
作者：
BRAMBLETT, GT;CHANG, S;FLAVIN, M
通讯作者：
FLAVIN, M
影响因子：
64.5
作者：
Engstler, Markus;Pfohl, Thomas;Overath, Peter
通讯作者：
Overath, Peter