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Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation.
The Journal of Biochemistry ( IF 2.7 ) Pub Date : 2020-04-11 , DOI: 10.1093/jb/mvaa019
Ran Wei 1 , Arika Sugiyama 1 , Yuta Sato 2 , Motohiro Nozumi 2 , Hironori Nishino 1 , Miyuki Takahashi 3 , Taro Saito 1 , Kanae Ando 1 , Mitsunori Fukuda 4 , Mineko Tomomura 5 , Michihiro Igarashi 2 , Shin-Ichi Hisanaga 1
Affiliation  

Lemur kinase 1 (LMTK1) is a membrane-bound Ser/Thr kinase that is expressed in neurons. There are two splicing variants of LMTK1 with different membrane binding modes, viz., cytosolic LMTK1A that binds to membranes through palmitoylation at the N-terminal cysteines and LMTK1B, an integral membrane protein with transmembrane sequences. We recently reported that LMTK1A regulates axon outgrowth and spine formation in neurons. However, data about LMTK1B are scarce. We analysed the expression and cellular localization of LMTK1B along with its role in axon and spine formation. We found that both LMTK1B and LMTK1A were expressed equally in the cerebral cortex and cerebellum of the mouse brain. Similar to LMTK1A, the wild type of LMTK1B was localized to Rab11-positive pericentrosomal compartment. The kinase negative (kn) mutant of LMTK1B was found to be associated with an increase in the tubular form of endoplasmic reticulum (ER), which was not the case with LMTK1A kn. Furthermore, unlike LMTK1A kn, LMTK1B kn did not stimulate the axon outgrowth and spine formation. These results suggest that while LMTK1A and LMTK1B share a common function in recycling endosomal trafficking at the pericentrosomal compartment, LMTK1B has an additional unique function in vesicle transport in the ER region.

中文翻译:

LMTK1A和LMTK1B的亚型依赖亚细胞定位及其在轴突生长和脊柱形成中的作用。

狐猴激酶1(LMTK1)是膜结合的Ser / Thr激酶,在神经元中表达。LMTK1有两个剪接变体,具有不同的膜结合模式,即胞质LMTK1A通过N端半胱氨酸的棕榈酰化作用与膜结合,而LMTK1B是具有跨膜序列的完整膜蛋白。我们最近报道,LMTK1A调节神经元中的轴突生长和脊柱形成。但是,有关LMTK1B的数据很少。我们分析了LMTK1B的表达和细胞定位及其在轴突和脊柱形成中的作用。我们发现LMTK1B和LMTK1A在小鼠大脑皮层和小脑中均表达。与LMTK1A相似,野生型LMTK1B定位于Rab11阳性的中心体周围区室。发现LMTK1B的激酶阴性(kn)突变体与管状内质网(ER)的增加有关,而LMTK1A kn并非如此。此外,与LMTK1A kn不同,LMTK1B kn不会刺激轴突生长和脊柱形成。这些结果表明,虽然LMTK1A和LMTK1B在回收中心体腔室的内体运输中具有共同的功能,但LMTK1B在ER区的囊泡运输中具有其他独特功能。
更新日期:2020-04-11
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