Myelin-Associated Glycoprotein Rescues Motoneurons From Apoptosis Via RhoA Signaling Pathway

ANABELA PALANDRI; ROZÉS SALVADOR, VICTORIA; EDUARDO GARBARINO-PICO; RONALD L. SCHNAAR; PABLO HECTOR HORACIO LOPEZ

Mendoza

Congreso; 48th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Myelin-associated glycoprotein (MAG) is a lectin present in the periaxonal layer of myelin that engages several axonal receptors, including Nogo-R (NgRs), which have a modulatory role on programmed cell death (PCD) of motoneurons (MNs) dependent on the activation of the neurotrophin receptor P75NTR. The small GTPaseRhoA regulates diverse cellular processes such as apoptosis, through one of the effector proteins, Rho-Kinase (ROCK). The aim of this study was to analyze a possible modulatory role of MAG on PCD of MNs and elucidate the signaling pathways associated with this effect. A time course study showed that early after birth Mag-null mice have a reduction in MNs count. Also Mag-null mice exhibit increased susceptibility in an in vivo model of PCD induced by a sciatic nerve crush. Interestingly pre-treatment with a soluble form of MAG (MAG-Fc) prevented MN apoptosis in this model. Studies using an in vitro model of P75NTR-dependent PCD on spinal cord organotypic cultures and a MN cell line confirmed the modulatory role of MAG. We further report the in vivo role of RhoA signaling pathway in the protective effect of MAG against MN death. Treatment with Y27632 to inhibit ROCK was sufficient to reverse the protective rol of MAG-Fc. These findings indicate that RhoAsignaling pathway plays a critical rol in the protective effect of MAG against PCD of MNs during development.