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Lifeguard/neuronal membrane protein 35 regulates Fas ligand‐mediated apoptosis in neurons via microdomain recruitment
Author(s) -
Fernández Miriam,
Segura Miguel F.,
Solé Carme,
Colino Alicia,
Comella Joan X.,
Ceña Valentín
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04767.x
Subject(s) - fas ligand , microbiology and biotechnology , biology , apoptosis , programmed cell death , lipid raft , cerebellum , caspase , fas receptor , signal transduction , neuroscience , biochemistry
Fas ligand (FasL)‐receptor system plays an essential role in regulating cell death in the developing nervous system, and it has been implicated in neurodegenerative and inflammatory responses in the CNS. Lifeguard (LFG) is a protein highly expressed in the hippocampus and the cerebellum, and it shows a particularly interesting regulation by being up‐regulated during postnatal development and in the adult. We show that over‐expression of LFG protected cortical neurons from FasL‐induced apoptosis and decreased caspase‐activation. Reduction of endogenous LFG expression by small interfering RNA sensitized cerebellar granular neurons to FasL‐induced cell death and caspase‐8 activation, and also increased sensitivity of cortical neurons. In differentiated cerebellar granular neurons, protection from FasL‐induced cell death could be attributed exclusively to LFG and appears to be independent of FLICE inhibitor protein. Thus, LFG is an endogenous inhibitor of FasL‐mediated neuronal death and it mediates the FasL resistance of CNS differentiated neurons. Finally, we also demonstrate that LFG is detected in lipid rafts microdomains, where it may interact with Fas receptor and regulate FasL‐activated signaling pathways.