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Related Concept Videos

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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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Highly Sensitive and Quantitative Detection of Proteins and Their Isoforms by Capillary Isoelectric Focusing Method
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EphB regulates L1 phosphorylation during retinocollicular mapping.

Jinxia Dai1, Jasbir S Dalal, Sonal Thakar

  • 1Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.

Molecular and Cellular Neurosciences
|May 15, 2012
PubMed
Summary

Ephrin-B kinases phosphorylate the L1 cell adhesion molecule, modulating its interaction with ankyrin. This phosphorylation is crucial for the correct topographic mapping of retinal ganglion cell axons in the brain.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • The cell adhesion molecule L1 is vital for the topographic mapping of retinal ganglion cell (RGC) axons to the superior colliculus (SC).
  • Abnormalities in L1 ankyrin-binding motifs (FIGQY(1229)H) lead to aberrant RGC axon mapping, similar to phenotypes observed in EphB receptor tyrosine kinase mutants.

Purpose of the Study:

  • To investigate the functional interaction between L1 and EphB receptors.
  • To determine if EphB kinases phosphorylate L1 at the ankyrin-binding site (FIGQY(1229)).

Main Methods:

  • Utilized HEK293 cells expressing L1 and EphB receptors to study phosphorylation.
  • Employed a phospho-specific antibody for tyrosine-phosphorylated FIGQY(1229) motif.
  • Generated L1-Y(1176)A knock-in mice and analyzed retinocollicular mapping.
  • Performed immunostaining and immunoblotting on mouse SC tissues.
  • Assessed neurite outgrowth in retinal explant cultures.

Main Results:

  • EphB2 kinase induced L1 phosphorylation at FIGQY(1229) and disrupted ankyrin recruitment in transfected cells.
  • Src family kinases mediated EphB2-induced L1 phosphorylation at FIGQY(1229).
  • EphB1 and EphB3 also mediated L1 phosphorylation at FIGQY(1229).
  • L1 phosphorylation at Tyrosine(1176) was unaffected by EphB2; L1-Y(1176)A mice showed normal mapping.
  • L1 colocalized with phospho-FIGQY in RGC axons within the SC.
  • L1 phosphorylation at FIGQY(1229) was reduced in EphB2/B3 mutant SC.
  • Inhibition of ankyrin binding in L1Y(1229)H mutant RGCs increased neurite outgrowth.

Conclusions:

  • EphB kinases phosphorylate L1 at FIGQY(1229), modulating L1-ankyrin binding.
  • This modulation is critical for the mediolateral retinocollicular topographic mapping.
  • L1-ankyrin binding appears to constrain RGC axon growth.