ArticleMolecular and cellular neurosciences2012
EphB regulates L1 phosphorylation during retinocollicular mapping.
Article in Molecular and cellular neurosciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 13 citations in OpenAlex.
- Ankyrin B promotes developmental spine regulation in the mouse prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Roles and mechanisms of ankyrin-G in neuropsychiatric disorders.Experimental & molecular medicine · 2022Review
- Wiring subcortical image-forming centers: Topography, laminar targeting, and map alignment.Current topics in developmental biology · 2021Review
- Neuroprotective Peptide NAPVSIPQ Antagonizes Ethanol Inhibition of L1 Adhesion by Promoting the Dissociation of L1 and Ankyrin-G.Biological psychiatry · 2020Article
- L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans.Development (Cambridge, England) · 2016Article
- The role of cell adhesion molecules in visual circuit formation: from neurite outgrowth to maps and synaptic specificity.Developmental neurobiology · 2015Review
- Multiple EphB receptors mediate dorsal-ventral retinotopic mapping via similar bi-functional responses to ephrin-B1.Molecular and cellular neurosciences · 2014Article
- Connecting the retina to the brain.ASN neuro · 2014Review
- Neuron glia-related cell adhesion molecule (NrCAM) promotes topographic retinocollicular mapping.PloS one · 2013Article
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9 authors at 5 institutions in 2 countries.
Funding
Abstract
Interaction of the cell adhesion molecule L1 with the cytoskeletal adaptor ankyrin is essential for topographic mapping of retinal ganglion cell (RGC) axons to synaptic targets in the superior colliculus (SC). Mice mutated in the L1 ankyrin-binding motif (FIGQY(1229)H) display abnormal mapping of RGC axons along the mediolateral axis of the SC, resembling mouse mutant phenotypes in EphB receptor tyrosine kinases. To investigate whether L1 functionally interacts with EphBs, we investigated the role of EphB kinases in phosphorylating L1 using a phospho-specific antibody to the tyrosine phosphorylated FIGQY(1229) motif. EphB2, but not an EphB2 kinase dead mutant, induced tyrosine phosphorylation of L1 at FIGQY(1229) and perturbed ankyrin recruitment to the membrane in L1-transfected HEK293 cells. Src family kinases mediated L1 phosphorylation at FIGQY(1229) by EphB2. Other EphB receptors that regulate medial-lateral retinocollicular mapping, EphB1 and EphB3, also mediated phosphorylation of L1 at FIGQY(1229). Tyrosine(1176) in the cytoplasmic domain of L1, which regulates AP2/clathrin-mediated endocytosis and axonal trafficking, was not phosphorylated by EphB2. Accordingly mutation of Tyr(1176) to Ala in L1-Y(1176)A knock-in mice resulted in normal retinocollicular mapping of ventral RGC axons. Immunostaining of the mouse SC during retinotopic mapping showed that L1 colocalized with phospho-FIGQY in RGC axons in retinorecipient layers. Immunoblotting of SC lysates confirmed that L1 was phosphorylated at FIGQY(1229) in wild type but not L1-FIGQY(1229)H (L1Y(1229)H) mutant SC, and that L1 phosphorylation was decreased in the EphB2/B3 mutant SC. Inhibition of ankyrin binding in L1Y(1229)H mutant RGCs resulted in increased neurite outgrowth compared to WT RGCs in retinal explant cultures, suggesting that L1-ankyrin binding serves to constrain RGC axon growth. These findings are consistent with a model in which EphB kinases phosphorylate L1 at FIGQY(1229) in retinal axons to modulate L1-ankyrin binding important for mediolateral retinocollicular topography.
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