LKB1 coordinates neurite remodeling to drive synapse layer emergence in the outer retina
| Autor: | Anna K. Casasent, Nicholas E. Albrecht, Melanie A. Samuel, Danye Jiang, Jonathan Alevy, Arlene A. Hirano, Courtney A. Burger, Justine H Liang, Nicholas C. Brecha |
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| Rok vydání: | 2020 |
| Předmět: |
Male
retina congenital hereditary and neonatal diseases and abnormalities Mouse Neurite VGLUT1 QH301-705.5 Neurogenesis Science Cell AMP-Activated Protein Kinases Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Synapse synapse Postsynaptic potential Neurites medicine Animals Photoreceptor Cells Biology (General) Axon skin and connective tissue diseases Mice Knockout axon Retina General Immunology and Microbiology Kinase Chemistry General Neuroscience RIBEYE General Medicine neuron Cell biology Protein Transport medicine.anatomical_structure Mutation Synapses Vesicular Glutamate Transport Protein 1 Medicine Female sense organs Neuron Research Article Neuroscience |
| Zdroj: | eLife, Vol 9 (2020) eLife |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.56931 |
| Popis: | Structural changes in pre and postsynaptic neurons that accompany synapse formation often temporally and spatially overlap. Thus, it has been difficult to resolve which processes drive patterned connectivity. To overcome this, we use the laminated outer murine retina. We identify the serine/threonine kinase LKB1 as a key driver of synapse layer emergence. The absence of LKB1 in the retina caused a marked mislocalization and delay in synapse layer formation. In parallel, LKB1 modulated postsynaptic horizontal cell refinement and presynaptic photoreceptor axon growth. Mislocalized horizontal cell processes contacted aberrant cone axons in LKB1 mutants. These defects coincided with altered synapse protein organization, and horizontal cell neurites were misdirected to ectopic synapse protein regions. Together, these data suggest that LKB1 instructs the timing and location of connectivity in the outer retina via coordinate regulation of pre and postsynaptic neuron structure and the localization of synapse-associated proteins. |
| Databáze: | OpenAIRE |
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