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  • MAG induces apoptosis in cerebellar granule neurons through p75NTR demarcating granule layer/white matter boundary.

MAG induces apoptosis in cerebellar granule neurons through p75NTR demarcating granule layer/white matter boundary.

Cell death & disease (2019-10-02)
Diana Fernández-Suárez, Favio A Krapacher, Annika Andersson, Carlos F Ibáñez, Lilian Kisiswa
ABSTRACT

MAG (Myelin-associated glycoprotein) is a type I transmembrane glycoprotein expressed by Schwann cells and oligodendrocytes, that has been implicated in the control of axonal growth in many neuronal populations including cerebellar granule neurons (CGNs). However, it is unclear whether MAG has other functions in central nervous system, in particular, in cerebellar development and patterning. We find that MAG expression in the cerebellum is compartmentalised resulting in increased MAG protein levels in the cerebellar white matter. MAG induces apoptosis in developing CGNs through p75NTR signalling. Deletion of p75NTR in vivo reduced the number of apoptotic neurons in cerebellar white matter during development leading to reduction in the size of white matter in the adulthood. Furthermore, we show that MAG impairs CGNs neurite outgrowth as consequence of MAG-induced apoptosis in CGNs. Mechanistically, we find that MAG/NgR1-induced cell death is dependent of p75NTR-mediated activation of JNK/cell death signalling pathway. Together, these findings identify the mechanisms by which MAG induces CGNs apoptotic activity, a crucial event that facilitates cerebellar layer refinement during development.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-GAPDH antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Potassium chloride, for molecular biology, ≥99.0%
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Poly-D-lysine hydrobromide, average mol wt 30,000-70,000, lyophilized powder, γ-irradiated, BioReagent, suitable for cell culture