title: The parkin-like human homolog of Drosophila ariadne-1 (HHARI) can induce aggresome formation in mammalian cells and is immunologically detectable in Lewy bodies.
abstract: Loss of functional Parkin is responsible for the death of midbrain dopaminergic neurons in human autosomal recessive juvenile parkinsonism. Since no cells express functional Parkin, it is unclear why other neuronal and non-neuronal populations are not also endangered. One possible explanation is that other neurons express a redundant ubiquitin-protein ligase (E3) that is absent from dopaminergic neurons. In this study, we demonstrate that human homolog of Drosophila ariadne-1 (HHARI) is a candidate for such a redundant function. In in vitro assays, HHARI binds to many of the same proteins as parkin, including CDCrel-1, synphilin-1, and CASK. In cell culture studies, HHARI forms aggresomes that are indistinguishable from those formed by parkin in terms of morphology, subcellular localization, incorporation of ubiquitin-proteasome components, and dependence on microtubules. In addition, endogenous HHARI is found in human Lewy bodies in both Parkinson's disease and diffuse Lewy body disorder. Taken together, these data suggest that HHARI, and perhaps other Parkin-like E3 ligases, may serve redundant roles for parkin in different cell types.
authors: Molecular and Cellular Biology Program, University of Massachusetts, Amherst, MA 01003, USA.
authors: Sangram S
authors: SS
authors: Parelkar
authors: Juan G
authors: JG
authors: Cadena
authors: Chul
authors: C
authors: Kim
authors: Zhaohui
authors: Z
authors: Wang
authors: Rachel
authors: R
authors: Sugal
authors: Brooke
authors: B
authors: Bentley
authors: Luis
authors: L
authors: Moral
authors: Helen C
authors: HC
authors: Ardley
authors: Lawrence M
authors: LM
authors: Schwartz
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