RGD Reference Report - Effect of gamma-synuclein silencing on apoptotic pathways in retinal ganglion cells. - Rat Genome Database

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Effect of gamma-synuclein silencing on apoptotic pathways in retinal ganglion cells.

Authors: Surgucheva, Irina  Shestopalov, Valery I  Surguchov, Andrei 
Citation: Surgucheva I, etal., J Biol Chem. 2008 Dec 26;283(52):36377-85. doi: 10.1074/jbc.M806660200. Epub 2008 Oct 20.
RGD ID: 13782255
Pubmed: PMID:18936092   (View Abstract at PubMed)
PMCID: PMC2606004   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M806660200   (Journal Full-text)

gamma-Synuclein (Syn G) is highly expressed in retinal ganglion cells and the loss of these cells in glaucoma is associated with significant reduction of the intracellular Syn G level. However, a causative relationship between these two events has not been established. Here we show that the knockdown of Syn G results in a decreased viability of the immortalized retinal ganglion cells (RGC-5). The Syn G silencing reduces phosphorylation of serine 112 (Ser112) in Bad protein, a member of the Bcl-2 family that plays a critical role in apoptotic cell death signaling. Our gene expression analysis data suggests that changes in Bad phosphorylation status may be caused by a coordinated shift in activities of kinases controlling Bad phosphorylation and phosphatases catalyzing its dephosphorylation. Moreover, increased phosphorylation of Bad-sequestering protein 14-3-3 detected in these cells is also pro-apoptotic. These results suggest that the homeostatic level of Syn G in RGC-5 cells is required for transcriptional regulation of protein kinases and phosphatases, controlling phosphorylation of Bad and 14-3-3. Lowering Syn G causes Bad dephosphorylation, dissociation from phosphorylated 14-3-3, and translocation to mitochondria where it initiates apoptotic death cascade.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of cellular response to stress  IMP 13782255 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sncg  (synuclein, gamma)


Additional Information