Neuron Glia-Related Cell Adhesion Molecule (NrCAM) Promotes Topographic Retinocollicular Mapping
| Autor: | Patricia F. Maness, Galina P. Demyanenko, Leann H. Brennaman, Mona Buhusi, Matthew B. Dalva, Jinxia Dai, Martin Hruska |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Retinal Ganglion Cells
Mouse L1 family lcsh:Medicine Biochemistry Mice 0302 clinical medicine Molecular Cell Biology Ankyrin Axon lcsh:Science Mice Knockout chemistry.chemical_classification 0303 health sciences Multidisciplinary Animal Models Axon Guidance Cell biology medicine.anatomical_structure Research Article Superior Colliculi Adhesion Molecules Immunoblotting Ankyrin binding Biology Signaling Pathways Retinal ganglion Retina Cell Line 03 medical and health sciences Model Organisms Developmental Neuroscience Cell Adhesion medicine Animals Humans Immunoprecipitation 030304 developmental biology lcsh:R Proteins Molecular Development Actin cytoskeleton Axons Anterograde tracing chemistry Cellular Neuroscience lcsh:Q Neural Circuit Formation Molecular Neuroscience Cell Adhesion Molecules 030217 neurology & neurosurgery Developmental Biology Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 9, p e73000 (2013) |
| DOI: | 10.17615/ythy-4p74 |
| Popis: | NrCAM (Neuron-glial related cell adhesion molecule), a member of the L1 family of cell adhesion molecules, reversibly binds ankyrin and regulates axon growth, but it has not been studied for a role in retinotopic mapping. During development of retino-collicular topography, NrCAM was expressed uniformly in retinal ganglion cells (RGCs) along both mediolateral and anteroposterior retinal axes, and was localized on RGC axons within the optic tract and superior colliculus (SC). Anterograde tracing of RGC axons in NrCAM null mutant mice at P10, when the map resembles its mature form, revealed laterally displaced ectopic termination zones (eTZs) of axons from the temporal retina, indicating defective mediolateral topography, which is governed by ephrinB/EphBs. Axon tracing at P2 revealed that interstitial branch orientation of ventral-temporal RGC axons in NrCAM null mice was compromised in the medial direction, likely accounting for displacement of eTZs. A similar retinocollicular targeting defect in EphB mutant mice suggested that NrCAM and EphB interact to regulate mediolateral retino-collicular targeting. We found that EphB2 tyrosine kinase but not an EphB2 kinase dead mutant, phosphorylated NrCAM at a conserved tyrosine residue in the FIGQY ankyrin binding motif, perturbing ankyrin recruitment in NrCAM transfected HEK293 cells. Furthermore, the phosphorylation of NrCAM at FIGQY in SC was decreased in EphB1/3 and EphB1/2/3 null mice compared to WT, while phospho-FIGQY of NrCAM in SC was increased in EphB2 constitutively active (F620D/F620D) mice. These results demonstrate that NrCAM contributes to mediolateral retinocollicular axon targeting by regulating RGC branch orientation through a likely mechanism in which ephrinB/EphB phosphorylates NrCAM to modulate linkage to the actin cytoskeleton. |
| Databáze: | OpenAIRE |
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