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Molecular Neurobiology

, Volume 55, Issue 9, pp 7164–7178 | Cite as

A Fragment of Adhesion Molecule L1 Binds to Nuclear Receptors to Regulate Synaptic Plasticity and Motor Coordination

  • Kristina Kraus
  • Ralf Kleene
  • Melad Henis
  • Ingke Braren
  • Hardeep Kataria
  • Ahmed Sharaf
  • Gabriele Loers
  • Melitta Schachner
  • David Lutz
Article

Abstract

Proteolytic cleavage of the neuronal isoform of the murine cell adhesion molecule L1, triggered by stimulation of the cognate L1-dependent signaling pathways, results in the generation and nuclear import of an L1 fragment that contains the intracellular domain, the transmembrane domain, and part of the extracellular domain. Here, we show that the LXXLL and FXXLF motifs in the extracellular and transmembrane domain of this L1 fragment mediate the interaction with the nuclear estrogen receptors α (ERα) and β (ERβ), peroxisome proliferator-activated receptor γ (PPARγ), and retinoid X receptor β (RXRβ). Mutations of the LXXLL motif in the transmembrane domain and of the FXXLF motif in the extracellular domain disturb the interaction of the L1 fragment with these nuclear receptors and, when introduced by viral transduction into mouse embryos in utero, result in impaired motor coordination, learning and memory, as well as synaptic connectivity in the cerebellum, in adulthood. These impairments are similar to those observed in the L1-deficient mouse. Our findings suggest that the interplay of nuclear L1 and distinct nuclear receptors is associated with synaptic contact formation and plasticity.

Keywords

Cell adhesion molecule L1CAM Nuclear receptors Motor coordination Cerebellar circuitry Synaptic plasticity 

Notes

Acknowledgements

We are grateful to Eva Kronberg for the excellent animal care and to Ute Bork and Dagmar Drexler for the excellent technical assistance.

Funding Information

D.L. is supported by a FFM fellowship of the Medical Faculty, University Medical Center Hamburg-Eppendorf. D.L. is grateful for the support by the Hertie Foundation. M.H. is supported by the Egyptian Cultural Bureau Berlin, Egyptian Ministry of Higher Education, and the Egyptian Missions Sector. M.S. is grateful for the support by the Li Kashing Foundation at Shantou University Medical College.

Compliance with Ethical Standards

Experiments were carried out and the manuscript was prepared following the ARRIVE guidelines for animal research [39].

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kristina Kraus
    • 1
  • Ralf Kleene
    • 1
  • Melad Henis
    • 2
    • 3
  • Ingke Braren
    • 4
  • Hardeep Kataria
    • 1
  • Ahmed Sharaf
    • 2
    • 5
  • Gabriele Loers
    • 1
  • Melitta Schachner
    • 6
    • 7
  • David Lutz
    • 1
    • 2
  1. 1.Arbeitsgruppe für Biosynthese Neuraler StrukturenUniversitätsklinikum Hamburg-EppendorfHamburgGermany
  2. 2.Institut für Strukturelle Neurobiologie, Universitätsklinikum Hamburg-EppendorfHamburgGermany
  3. 3.Department of Anatomy and Histology, Faculty of Veterinary MedicineAssiut UniversityAssiutEgypt
  4. 4.Vector Core UnitInstitut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-EppendorfHamburgGermany
  5. 5.Department of Histology and Cytology, Faculty of Veterinary MedicineZagazig UniversityZagazigEgypt
  6. 6.Keck Center for Collaborative Neuroscience and Department of Cell Biology and NeuroscienceRutgers UniversityPiscatawayUSA
  7. 7.Center for NeuroscienceShantou University Medical CollegeShantouChina

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