The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells
Summary: 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 orc...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718313007 |
| _version_ | 1819290205918593024 |
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| author | Ken-ichiro Kuwako Hideyuki Okano |
| author_facet | Ken-ichiro Kuwako Hideyuki Okano |
| author_sort | Ken-ichiro Kuwako |
| collection | DOAJ |
| description | Summary: 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. Keywords: dendrite, self-avoidance, Purkinje cell, cerebellum, LKB1, SIK, Robo2 |
| first_indexed | 2024-12-24T03:19:03Z |
| format | Article |
| id | doaj.art-17b98314afe941979302be18cbf60c16 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-24T03:19:03Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-17b98314afe941979302be18cbf60c162022-12-21T17:17:32ZengElsevierCell Reports2211-12472018-09-01241128082818.e4The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje CellsKen-ichiro Kuwako0Hideyuki Okano1Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding authorDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanSummary: 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. Keywords: dendrite, self-avoidance, Purkinje cell, cerebellum, LKB1, SIK, Robo2http://www.sciencedirect.com/science/article/pii/S2211124718313007 |
| spellingShingle | Ken-ichiro Kuwako Hideyuki Okano The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells Cell Reports |
| title | The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells |
| title_full | The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells |
| title_fullStr | The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells |
| title_full_unstemmed | The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells |
| title_short | The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells |
| title_sort | lkb1 sik pathway controls dendrite self avoidance in purkinje cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718313007 |
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