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

作者：Kraus, Kristina; Kleene, Ralf; Henis, Melad; Braren, Ngke; Kataria, Hardeep; Sharaf, Ahmed; Loers, Gabriele; Schachner, Melitta^*; Lutz, David^*

来源：Molecular Neurobiology, 2018, 55(9): 7164-7178.

DOI：10.1007/s12035-018-0901-7

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

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 alpha (ER alpha) and beta (ER beta), peroxisome proliferator-activated receptor gamma (PPAR gamma), and retinoid X receptor beta (RXR beta). 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.

• 出版日期2018-9
• 单位rutgers; 汕头大学