NMDA Receptors (NMDA-Rs) are ionotropic glutamate receptors, which associate with LDL Receptor-related Protein-1 (LRP1) to trigger cell-signaling in response to protein ligands in neurons. Herein, we demonstrate for the first time that the NMDA-R is expressed by rat Schwann cells (SCs) and functions independently and with LRP1 to regulate SC physiology. The NR1 and NR2b NMDA-R subunits were expressed by cultured SCs and up-regulated in sciatic nerves following crush injury. The ability of LRP1 ligands to activate ERK1/2 and promote SC migration required the NMDA-R. NR1 gene-silencing compromised SC survival. Injection of the LRP1 ligands, tissue-type plasminogen activator (tPA) or MMP9-PEX, into crush-injured sciatic nerves, activated ERK1/2 in SCs in vivo and the response was blocked by systemic treatment with the NMDA-R inhibitor, MK801. tPA was unique amongst the LRP1 ligands examined because tPA activated cell-signaling and promoted SC migration by interacting with the NMDA-R independently of LRP1, albeit with delayed kinetics. These results define the NMDA-R as a SC signaling receptor for protein ligands and a major regulator of SC physiology, which may be particularly important in PNS injury.
The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell survival and migration / Mantuano, Elisabetta; Lam, Michael S; Shibayama, Masataka; Campana, W. Marie; Gonias, Steven L.. - In: JOURNAL OF CELL SCIENCE. - ISSN 0021-9533. - ELETTRONICO. - 128:16(2015). [10.1242/jcs.173765]
The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell survival and migration
MANTUANO, ELISABETTA;
2015
Abstract
NMDA Receptors (NMDA-Rs) are ionotropic glutamate receptors, which associate with LDL Receptor-related Protein-1 (LRP1) to trigger cell-signaling in response to protein ligands in neurons. Herein, we demonstrate for the first time that the NMDA-R is expressed by rat Schwann cells (SCs) and functions independently and with LRP1 to regulate SC physiology. The NR1 and NR2b NMDA-R subunits were expressed by cultured SCs and up-regulated in sciatic nerves following crush injury. The ability of LRP1 ligands to activate ERK1/2 and promote SC migration required the NMDA-R. NR1 gene-silencing compromised SC survival. Injection of the LRP1 ligands, tissue-type plasminogen activator (tPA) or MMP9-PEX, into crush-injured sciatic nerves, activated ERK1/2 in SCs in vivo and the response was blocked by systemic treatment with the NMDA-R inhibitor, MK801. tPA was unique amongst the LRP1 ligands examined because tPA activated cell-signaling and promoted SC migration by interacting with the NMDA-R independently of LRP1, albeit with delayed kinetics. These results define the NMDA-R as a SC signaling receptor for protein ligands and a major regulator of SC physiology, which may be particularly important in PNS injury.File | Dimensione | Formato | |
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