Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation
Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation
复制标题
LMTK1A 和 LMTK1B 的异构体依赖性亚细胞定位及其在轴突生长和脊柱形成中的作用
DOI：
10.1093/jb/mvaa019
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Hisanaga Shin-ichi
中科院分区：
文献类型：
--
作者：
Wei Ran;Sugiyama Arika;Sato Yuta;Nozumi Motohiro;Nishino Hironori;Takahashi Miyuki;Saito Taro;Ando Kanae;Fukuda Mitsunori;Tomomura Mineko;Igarashi Michihiro;Hisanaga Shin-ichi
狐猴激酶1（LMTK 1）是一种在神经元中表达的膜结合的Ser/Thr激酶。有两种具有不同膜结合模式的LMTK 1剪接变体，即，胞质LMTK 1A通过N-末端半胱氨酸的棕榈酰化与膜结合，LMTK 1B是一种具有跨膜序列的完整膜蛋白。我们最近报道了LMTK 1A调节神经元中轴突生长和棘形成。然而，关于LMTK 1B的数据很少。我们分析了LMTK 1 B沿着的表达和细胞定位及其在轴突和棘形成中的作用。我们发现LMTK 1B和LMTK 1A在小鼠大脑的大脑皮层和小脑中表达相等。与LMTK 1A相似，野生型LMTK 1B定位于Rab 11阳性的近核粒体区室。发现LMTK 1B的激酶阴性（kn）突变体与内质网（ER）的管状形式的增加相关，而LMTK 1A kn的情况并非如此。此外，与LMTK 1A kn不同，LMTK 1B kn不刺激轴突生长和棘形成。这些结果表明，虽然LMTK 1A和LMTK 1B共享一个共同的功能，再循环内体运输在pericentrosomal区室，LMTK 1B有一个额外的独特功能，囊泡运输在ER区域。
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.