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

Ran Wei, Arika Sugiyama, Yuta Sato, Motohiro Nozumi, Hironori Nishino, Miyuki Takahashi, Taro Saito, Kanae Ando, Mitsunori Fukuda, Mineko Tomomura, Michihiro Igarashi, Shin Ichi Hisanaga

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)23-32
Number of pages10
JournalJournal of biochemistry
Volume168
Issue number1
DOIs
Publication statusPublished - 2020 Jul 1

Keywords

  • axon outgrowth
  • endoplasmic reticulum
  • endosome trafficking
  • LMTK1
  • Rab

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Wei, R., Sugiyama, A., Sato, Y., Nozumi, M., Nishino, H., Takahashi, M., Saito, T., Ando, K., Fukuda, M., Tomomura, M., Igarashi, M., & Hisanaga, S. I. (2020). Isoform-dependent subcellular localization of LMTK1A and LMTK1B and their roles in axon outgrowth and spine formation. Journal of biochemistry, 168(1), 23-32. https://doi.org/10.1093/jb/mvaa019