The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells

Ken ichiro Kuwako, Hideyuki Okano

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Strictly controlled dendrite patterning underlies precise neural connection. Dendrite self-avoidance is a crucial system preventing self-crossing and clumping of dendrites. Although many cell-surface molecules that regulate self-avoidance have been identified, the signaling pathway that orchestrates it remains poorly understood, particularly in mammals. Here, we demonstrate that the LKB1-SIK kinase pathway plays a pivotal role in the self-avoidance of Purkinje cell (PC) dendrites by ensuring dendritic localization of Robo2, a regulator of self-avoidance. LKB1 is activated in developing PCs, and PC-specific deletion of LKB1 severely disrupts the self-avoidance of PC dendrites without affecting gross morphology. SIK1 and SIK2, downstream kinases of LKB1, mediate LKB1-dependent dendrite self-avoidance. Furthermore, loss of LKB1 leads to significantly decreased Robo2 levels in the dendrite but not in the cell body. Finally, restoration of dendritic Robo2 level via overexpression largely rescues the self-avoidance defect in LKB1-deficient PCs. These findings reveal an LKB1-pathway-mediated developmental program that establishes dendrite self-avoidance. Kuwako and Okano show that the LKB1-SIK axis is essential for establishing dendrite self-avoidance in Purkinje cells by ensuring an appropriate level of dendritic Robo2. This study reveals a pivotal role for the LKB1 kinase pathway in the developmental program orchestrating the spatial configuration of dendrites in mammalian brain.

Original languageEnglish
Pages (from-to)2808-2818.e4
JournalCell Reports
Volume24
Issue number11
DOIs
Publication statusPublished - 2018 Sep 11

Keywords

  • cerebellum
  • dendrite
  • LKB1
  • Purkinje cell
  • Robo2
  • self-avoidance
  • SIK

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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