Tracking in the Wlds--the hunting of the SIRT and the luring of the Draper.
Wallerian degeneration of distal axons after nerve injury is significantly delayed in the Wlds mutant mouse. The Wlds protein is a fusion of nicotinamide mononucleotide adenyltransferase-1 (Nmnat1), an essential enzyme in the biosynthesis pathway of nicotinamide adenine dinucleotide (NAD), with the N-terminal 70 amino acids of the Ube4b ubiquitination assembly factor. The mechanism of Wlds action is still enigmatic, although recent efforts suggest that it is indirect and requires sequences flanking or linking the two fused open reading frames. Three papers in this issue of Neuron now show that Wlds action is conserved in Drosophila and that a critical role of Wlds may be the suppression of axonal self-destruct signals that induce Draper-mediated clearance of damaged axons by glial cells.
Fainzilber
Mike
M
Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel. mike.fainzilber@weizmann.ac.il
Twiss
Jeffery L
JL
D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000737:chemistry / Q000502:physiology; D037761:Sirtuins / Q000737:chemistry / Q000502:physiology*; D014855:Wallerian Degeneration / Q000378:metabolism / Q000503:physiopathology
D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C442580:Wld protein, mouse; C495322:drpr protein, Drosophila; C484007:NMNAT1 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D037761:Sirtuins