Products/Services Used | Details | Operation |
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Custom Vector Construction> | A GFP-tagged SARM1 SAMTIR DNA construct (Residues 412–724, Uniprot) in a pcDNA3.1(+) vector was ordered by custom synthesis from GenScript | Get A Quote |
Sterile alpha and toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is a neuronally expressed NAD glycohydrolase whose activity is increased in response to stress. NAD depletion triggers axonal degeneration, which is a characteristic feature of neurological diseases. Notably, loss of SARM1 is protective in murine models of peripheral neuropathy and traumatic brain injury. Herein, we report that citrate induces a phase transition that enhances SARM1 activity by ~2000-fold. This phase transition can be disrupted by mutating a residue involved in multimerization, G601P. This mutation also disrupts puncta formation in cells. We further show that citrate induces axonal degeneration in that is depen... More