Evidence for sequestration of polyglutamine inclusions by Drosophila myeloid leukemia factor.

Intracellular inclusions of abnormally long polyglutamine tracts and neurotoxicity are the hallmarks of several hereditary neurodegenerative disorders, including Huntington's disease (HD). In Drosophila melanogaster, dMLF, an ortholog of human myeloid leukemia factors, hMLF1 and hMLF2, suppressed polyglutamine toxicity and colocalized with the inclusions. In transfected primary rat neuronal cultures, dMLF and its orthologs reduced the morphological phenotypes and inclusions. Furthermore, dMLF reduced the recruitment of CBP and Hsp70 into the inclusions, both of which are among many essential proteins apparently trapped in the inclusions. These data suggest that a possible mechanism of suppression by dMLF is via the sequestration of polyglutamine oligomers or inclusions.