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- W1485223851 abstract "Lectins are of emerging importance for quality control and intracellular transport of glycoproteins in mammalian cells. One of the most prominent lectins involved in intracellular transport is ERGIC-53, which belongs to the family of L-type lectins. ERGIC-53 mediates the ER export of several glycoproteins like cathepsin Z, α1-antitrypsin (α1-AT) or blood coagulation factors. VIP36 belongs to the same family as ERGIC-53, but its cellular function remains poorly understood. VIP36 is a type I membrane protein. It cycles within the early secretory pathway and binds high mannose glycans. In order to gain insight into the function of VIP36 we decided to search for a luminal interaction partner for VIP36. We used a YFP-protein fragmentation complementation (YFP-PCA) based FACS screen of a human adult liver library to unravel an interaction partner for VIP36. Complementation of YFP is irreversible. Therefore, the YFP-PCA is well suited to detect weak interactions, like those between mammalian lectins and glycoproteins. YFP2-VIP36 was used as the bait in our screen. The human liver library was tagged with YFP1. Our screen identified α1-AT as an interaction partner for VIP36. VIP36 recognized high mannose containing α1-AT, which is consistent with the previously obtained results about the glycan affinity of VIP36. This interaction was increased upon inhibition of complex glycosylation by kifunensine. The complex formed by α1-AT and VIP36 was localized to the Golgi and the ER. α1-AT was previously identified as a cargo for ERGIC-53. Knockdown of ERGIC-53 slowed down α1-AT transport, consistent with a role for ERGIC-53 in ER export of α1-AT. In contrast, knockdown of VIP36 accelerated transport of endogenous α1-AT in HepG2 cells. This effect was specific for α1-AT, as the non-glycosylated protein albumin showed no acceleration in transport. In addition, VIP36 knockdown did not affect general protein secretion. This finding makes it unlikely that VIP36 acts as an anterograde cargo receptor for α1-AT. Further studies on the dynamics of the complex formed by VIP36 and α1-AT revealed that VIP36 recycles α1-AT back to the ER, which argues for a role of VIP36 in post-ER quality control. This notion is further supported by the finding that the chaperone BiP co-immunoprecipitated with the complex of VIP36 and α1-AT. This chaperone was previously described as an interaction partner for VIP36. This argues for a complex consisting of VIP36 and BiP acting together in post-ER quality control to detect misfolded α1-antitrypsin in the Golgi and retrieve it back to the ER. Apart from searching for an interaction partner, I also determined the effect of depletion of VIP36 on the morphology of the secretory pathway. The rationale behind this is the observation that cargo receptors contribute to the structural integrity of organelles of the secretory pathway. Knockdown of VIP36 had no effect on ER exit sites or on the ERGIC. However, VIP36 knockdown resulted in fragmentation of the Golgi apparatus. The fragmented Golgi was not the consequence of disturbed bidirectional protein transport and not due to effects on microtubules. Knockdown of VIP36 reduced COPI staining on the Golgi. VIP36 is likely to provide COPI binding sites on the Golgi via its cytosolic tail and thereby contribute to Golgi structural integrity. Our results underscore the importance of cargo receptors, not only for intracellular transport within the secretory pathway, but also to maintain the integrity of the secretory pathway itself.In conclusion, my thesis provides a deeper insight into the function of VIP36 in the early secretory pathway." @default.
- W1485223851 created "2016-06-24" @default.
- W1485223851 creator A5004877937 @default.
- W1485223851 date "2010-01-01" @default.
- W1485223851 modified "2023-10-02" @default.
- W1485223851 title "The role of the lectin VIP36 in the early secretory pathway" @default.
- W1485223851 cites W120703973 @default.
- W1485223851 cites W145497325 @default.
- W1485223851 cites W1481795283 @default.
- W1485223851 cites W1482605569 @default.
- W1485223851 cites W1482931197 @default.
- W1485223851 cites W1496241100 @default.
- W1485223851 cites W1498310106 @default.
- W1485223851 cites W1499112972 @default.
- W1485223851 cites W1499181135 @default.
- W1485223851 cites W1503628938 @default.
- W1485223851 cites W1507838062 @default.
- W1485223851 cites W1508005690 @default.
- W1485223851 cites W1516251834 @default.
- W1485223851 cites W1522422264 @default.
- W1485223851 cites W1522741331 @default.
- W1485223851 cites W1526263287 @default.
- W1485223851 cites W1527254461 @default.
- W1485223851 cites W1531818302 @default.
- W1485223851 cites W1543822556 @default.
- W1485223851 cites W1543918069 @default.
- W1485223851 cites W1546139069 @default.
- W1485223851 cites W1551925458 @default.
- W1485223851 cites W1551952768 @default.
- W1485223851 cites W1556859285 @default.
- W1485223851 cites W1557907946 @default.
- W1485223851 cites W1558413316 @default.
- W1485223851 cites W1559780107 @default.
- W1485223851 cites W1563724009 @default.
- W1485223851 cites W1565504291 @default.
- W1485223851 cites W1567855625 @default.
- W1485223851 cites W1570988466 @default.
- W1485223851 cites W1580875833 @default.
- W1485223851 cites W1582703272 @default.
- W1485223851 cites W1593869902 @default.
- W1485223851 cites W1594381485 @default.
- W1485223851 cites W1599583199 @default.
- W1485223851 cites W1607176255 @default.
- W1485223851 cites W1641104439 @default.
- W1485223851 cites W1668688100 @default.
- W1485223851 cites W1696710043 @default.
- W1485223851 cites W1717442359 @default.
- W1485223851 cites W1750780172 @default.
- W1485223851 cites W1757503351 @default.
- W1485223851 cites W1807853464 @default.
- W1485223851 cites W1820870565 @default.
- W1485223851 cites W1821925018 @default.
- W1485223851 cites W1844204379 @default.
- W1485223851 cites W1848205174 @default.
- W1485223851 cites W1861594661 @default.
- W1485223851 cites W1885047062 @default.
- W1485223851 cites W1919835673 @default.
- W1485223851 cites W1933295708 @default.
- W1485223851 cites W1943315667 @default.
- W1485223851 cites W1945261349 @default.
- W1485223851 cites W1946018878 @default.
- W1485223851 cites W1950671087 @default.
- W1485223851 cites W1950899592 @default.
- W1485223851 cites W1961885048 @default.
- W1485223851 cites W1963051938 @default.
- W1485223851 cites W1964702288 @default.
- W1485223851 cites W1964706050 @default.
- W1485223851 cites W1964906411 @default.
- W1485223851 cites W1965169361 @default.
- W1485223851 cites W1965839025 @default.
- W1485223851 cites W1966398753 @default.
- W1485223851 cites W1967055803 @default.
- W1485223851 cites W1967436528 @default.
- W1485223851 cites W1968066219 @default.
- W1485223851 cites W1968350043 @default.
- W1485223851 cites W1969421148 @default.
- W1485223851 cites W1971170718 @default.
- W1485223851 cites W1972348623 @default.
- W1485223851 cites W1972879829 @default.
- W1485223851 cites W1973229188 @default.
- W1485223851 cites W1973465923 @default.
- W1485223851 cites W1974004166 @default.
- W1485223851 cites W1974879832 @default.
- W1485223851 cites W1976389898 @default.
- W1485223851 cites W1976981613 @default.
- W1485223851 cites W1977186059 @default.
- W1485223851 cites W1977606211 @default.
- W1485223851 cites W1978014671 @default.
- W1485223851 cites W1978552910 @default.
- W1485223851 cites W1978911202 @default.
- W1485223851 cites W1979158821 @default.
- W1485223851 cites W1981515291 @default.
- W1485223851 cites W1981625315 @default.
- W1485223851 cites W1982432510 @default.
- W1485223851 cites W1983155917 @default.
- W1485223851 cites W1983621817 @default.
- W1485223851 cites W1983986068 @default.
- W1485223851 cites W1984347348 @default.
- W1485223851 cites W1984672567 @default.
- W1485223851 cites W1985860624 @default.