FIGURE 8.

Model of the MVB-dependent pathway for the transport of misfolded Wsc1p. A, normally, misfolded Wsc1p exits the ER and transits through the Golgi apparatus. It is next sorted to the MVB pathway and degraded in its entirety within the vacuolar lumen. This mechanism requires the ubiquitin ligase Rsp5p and ubiquitination of the Wsc1p cytoplasmic domain. B, misfolded GQC substrates missorted to the vacuolar limiting membrane. Degradation proceeds but is constrained by the membrane, leading to partial degradation products still integrated in the membrane. These aberrant products disrupt vacuolar membranes, which can lead to cell death.