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First published online January 12, 2006
doi: 10.1242/10.1242/jcs.02749

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Quality control of a mutant plasma membrane ATPase: ubiquitylation prevents cell-surface stability

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 830 N. University, Ann Arbor, MI 48109, USA

^* Author for correspondence (e-mail: amychang{at}umich.edu)

Accepted 19 October 2005

The plasma membrane ATPase, Pma1, has remarkable longevity at the cell surface. In contrast to the wild-type protein, the temperature-sensitive mutant Pma1-10 is misfolded and undergoes rapid removal from the cell surface for vacuolar degradation. At the restrictive temperature, Pma1-10 becomes ubiquitylated before or upon arrival at the plasma membrane. Internalization from the plasma membrane and vacuolar degradation of Pma1-10 is dependent on the ubiquitin-interacting motif (UIM) of the epsin Ent1, suggesting recognition of ubiquitylated substrate by the endocytic machinery. Surprisingly, ubiquitylation of Pma1-10 is reversed when its internalization is blocked in an end3 mutant. Under these conditions, Pma1-10 acquires association with detergent-insoluble, glycolipid-enriched complexes (DIGs) which has been suggested to promote stability of wild-type Pma1. Ubiquitylation does not cause DIG exclusion because a Pma1-Ub fusion protein is not significantly excluded from DIGs. We suggest that ubiquitylation of Pma1-10 represents a component of a quality control mechanism that targets the misfolded protein for removal from the plasma membrane. Rapid internalization of Pma1-10 caused by its ubiquitylation may preempt establishment of stabilizing interactions.

Key words: Ubiquitylation, Quality control, Plasma membrane ATPase

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