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LMTK1A 和 LMTK1B 的异构体依赖性亚细胞定位及其在轴突生长和棘突形成中的作用。

Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation.

机构信息

Department of Biological Sciences, Faculty of Sciences, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.

Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi, Chuo-ku, Niigata 951-8510, Japan.

出版信息

J Biochem. 2020 Jul 1;168(1):23-32. doi: 10.1093/jb/mvaa019.

DOI:10.1093/jb/mvaa019
PMID:32044995
Abstract

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.

摘要

Lemur 激酶 1(LMTK1)是一种表达在神经元中的膜结合丝氨酸/苏氨酸激酶。LMTK1 有两种不同的膜结合方式的剪接变体,即通过 N 端半胱氨酸的棕榈酰化与膜结合的胞质 LMTK1A 和具有跨膜序列的完整膜蛋白 LMTK1B。我们最近报道 LMTK1A 调节神经元中的轴突生长和棘突形成。然而,关于 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棘突形成中的作用。我们发现 LMTK1B 和 LMTK1A 在小鼠大脑的大脑皮层和小脑中有相同的表达。与 LMTK1A 相似,野生型 LMTK1B 定位于 Rab11 阳性中心体周质区室。激酶阴性(kn)突变体 LMTK1B 与内质网(ER)管状形式的增加有关,而 LMTK1A kn 则没有。此外,与 LMTK1A kn 不同,LMTK1B kn 不会刺激轴突生长和棘突形成。这些结果表明,虽然 LMTK1A 和 LMTK1B 在中心体周质区室的再循环内体运输中具有共同功能,但 LMTK1B 在 ER 区域的囊泡运输中具有额外的独特功能。

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Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation.LMTK1A 和 LMTK1B 的异构体依赖性亚细胞定位及其在轴突生长和棘突形成中的作用。
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