Impairment of autophagosome-lysosome fusion in the buff mutant @entity19 with the @entity72077 ( XXXX ) mutation.

@entity1 @entity72084 @entity72083 @entity146 @entity19 @entity1131 @entity72079 @entity55552 @entity72077 @entity72082 @entity72080 @entity72081 @entity72078 @entity72076 @entity72085
UNASSIGNED: The @entity1131 ( @entity1131 ) complex functions in endocytic and autophagic pathways in both lower eukaryotes and @entity1 cells through its involvement in fusion events between endosomes and lysosomes or autophagosomes and lysosomes. However, the differential molecular mechanisms underlying these fusion processes are largely unknown. Buff (bf) is a @entity19 mutant that carries an @entity72076 point mutation ( @entity72076 ) in the @entity72077 protein, a tethering protein and a core subunit of the @entity1131 complex. Bf @entity19 showed @entity146 , motor learning, and autophagic activity. Although the gross anatomy of the brain was apparently normal, the number of Purkinje cells was significantly reduced. Furthermore, we found that fusion between autophagosomes and lysosomes was defective in bf cells without compromising the endocytic pathway. The direct association of mutant @entity72077 ( @entity72076 ) with the autophagic SNARE complex, @entity72078 ( @entity72078 )- @entity72079 - @entity72080 , was enhanced. In addition, the @entity72077 ( @entity72076 ) mutation enhanced interactions with other @entity1131 subunits, namely @entity55552 , @entity72081 , @entity72082 , and @entity72083 , except for @entity72084 . Reduction of the interactions between @entity72077 ( @entity72085 ) and several other @entity1131 subunits led to decreased association with @entity72078 . These results suggest that the @entity72077 ( @entity72076 ) mutation plays dual roles by increasing the @entity1131 complex assembly and its association with the autophagic SNARE complex, which selectively affects the autophagosome-lysosome fusion that impairs basal autophagic activity and induces Purkinje cell loss.
