September 19, 2012

How ‘Jedi’ disposes of dead neurons

The protein Syk is essential for clearing away neuron “corpses” in the developing peripheral nervous system.

(Wellcome Images)

About half of the peripheral neurons generated during embryonic development die by a controlled cell death process. This pruning is necessary for normal development, but the neuronal “corpses” need to be cleared to prevent an inflammatory response (which could lead to autoimmune disease).

Bruce Carter, Ph.D., professor of Biochemistry, and colleagues previously showed that glial precursor cells, and two receptors they express (Jedi-1 and MEGF10), have an essential role in clearing dead neurons. Now, led by graduate student Jami Scheib, they report in the Sept. 19 Journal of Neuroscience that Jedi-1 and MEGF10 both activate a protein kinase called Syk, which promotes rearrangement of the cell cytoskeleton. They identified the Syk interaction domain in the receptors and showed that phosphorylation of this domain by Src family proteins enhanced receptor interaction with and activation of Syk. Inhibition of Syk in glial cells reduced the cells’ ability to clear dying neurons.

The results identify Syk as an essential mediator of Jedi-1 and MEGF10 signaling, which are required for clearing away neuron corpses in the developing peripheral nervous system.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke (NS064278) and the National Institute of Diabetes and Digestive and Kidney Diseases (DK000563) of the National Institutes of Health.