BPAG1a and b associate with EB1 and EB3 and modulate vesicular transport, Golgi apparatus structure, and cell migration in C2.7 myoblasts.
BPAG1a and b associate with EB1 and EB3 and modulate vesicular transport, Golgi apparatus structure, and cell migration in C2.7 myoblasts.
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DOI：
10.1371/journal.pone.0107535
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Borradori L
中科院分区：
文献类型：
--
作者：
Poliakova K;Adebola A;Leung CL;Favre B;Liem RK;Schepens I;Borradori L
BPAG1a和BPAG1b(BPAG1a/b)是DST基因编码的两种主要亚型，与MACF1a和MACF1b有同源性。这些蛋白质是Plakin家族的成员，是一种巨大的多模块蛋白质，能够将中间丝、微管和微丝细胞骨架网络相互连接并连接到不同的细胞膜位置。它们也是调节细胞骨架动力学的信号蛋白的支架。为了更好地了解BPAG1a/b的功能，我们进一步鉴定了它们与微管相互作用的重要C末端区域，并评估了这些异构体在c2.7成肌细胞细胞骨架组织中的作用。我们的结果表明，与先前报道的那样，DST和Macf1前-mRNAs的5‘端不仅发生了选择性剪接，而且它们的3’端也发生了选择性剪接，导致了BPAG1和MACF1的另外四个mRNA变体的表达。这些异构体特异的C-尾巴能够捆绑微管并与EB1和EB3结合，这是两个微管和末端蛋白。在C2.7细胞系中，BPAG1a/b的敲除对微管和微丝网络的组织没有重大影响，但对内吞作用和高尔基体结构的维持有负面影响，高尔基体结构变得分散。最后，BPAG1a/b的敲除导致细胞迁移的直接性降低，但不损害细胞的初始黏附。这些数据为DST前mRNAs选择性剪接的复杂性以及BPAG1a/b在囊泡运输、高尔基体结构以及C2.7成肌细胞迁移中的作用提供了新的见解。
BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5′ end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3′ end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts.
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影响因子：
3.3
作者：
Applewhite DA;Grode KD;Keller D;Zadeh AD;Slep KC;Rogers SL
通讯作者：
Rogers SL
DOI：
10.1083/jcb.118.6.1333
发表时间：
1992-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Corthésy-Theulaz I;Pauloin A;Pfeffer SR
通讯作者：
Pfeffer SR
影响因子：
4.4
作者：
Bhanot, Kunal;Young, Kevin G.;Kothary, Rashmi
通讯作者：
Kothary, Rashmi
影响因子：
3.3
作者：
Applewhite DA;Grode KD;Duncan MC;Rogers SL
通讯作者：
Rogers SL
影响因子：
9.2
作者：
Drabek, Ksenija;van Ham, Marco;Galjart, Niels
通讯作者：
Galjart, Niels