RT Journal Article
SR Electronic
T1 A post-ER degradation pathway that relies on protease-dependent internalization from the vacuolar membrane
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 778530
DO 10.1101/778530
A1 Leticia Lemus
A1 Zrinka Matić
A1 Veit Goder
YR 2019
UL http://biorxiv.org/content/early/2019/09/22/778530.abstract
AB Newly synthesized proteins of the secretory pathway are quality-controlled inside the endoplasmic reticulum (ER) and, if not properly folded, are retained. An exception are glycosylphosphatidylinositol-anchored proteins (GPI-APs) which can leave the ER even when misfolded and are routed to the vacuole/lysosome for degradation by largely unknown mechanisms linked to post-ER quality control. Using yeast as model organism, we show that Gas1*, an ER-exported misfolded GPI-AP, is diverted from the secretory pathway to endosomes for transport to the vacuole. However, Gas1* is not sorted into endosomal intraluminal vesicles but internalizes directly from the vacuolar membrane. There, the vacuolar protease Pep4, but not any other known vacuolar protease, is required for Gas1* internalization. Our data reveal novel and unexpected mechanisms for invaginations from the vacuolar membrane.HighlightsER-exited misfolded GPI-anchored proteins are routed to the vacuole via endosomes but do not internalize into intraluminal vesiclesInternalization occurs directly from the vacuolar membrane into intravacuolar mobile structuresInternalization from the vacuolar membrane depends on the proteolytic activity of the vacuolar protease Pep4