Cell Biology

Meet U at the Terminal

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Science  29 Jan 2010:
Vol. 327, Issue 5965, pp. 505
DOI: 10.1126/science.327.5965.505-b

Parkinson's disease is characterized by progressive neurodegeneration and has been linked to mutations in the gene parkin, which encodes a protein that recruits enzymes that catalyze the conjugation of ubiquitin to target substrates. Parkin itself contains a ubiquitin-like (Ubl) domain, which is structurally similar to ubiquitin but is not rich in proline residues. The Src homology 3 (SH3) domain is found in hundreds of copies in the human proteome, and it was originally discovered as a mediator of protein-protein interactions, particularly via its affinity for proline-rich regions. Trempe et al. have found that the Ubl domain in parkin binds to the SH3 domain in endophilin A, which is involved in the retrieval of synaptic vesicles during neuronal activity. Phosphorylation increased the interaction of parkin with endophilin A, and also stimulated the ubiquitination of a group of proteins in synaptic nerve terminals in wild-type mice, but not in parkin-deficient animals. Thus, a regulated interaction between ubiquitination and endocytosis may provide a clue to the pathophysiology in patients with Parkinson's disease.

Mol. Cell 36, 1034 (2009).

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