000133540 001__ 133540
000133540 005__ 20180317095225.0
000133540 0247_ $$2doi$$a10.1073/pnas.0710389105
000133540 02470 $$2DAR$$a12553
000133540 02470 $$2ISI$$a000254893600020
000133540 037__ $$aARTICLE
000133540 245__ $$aPalmitoylation and ubiquitination regulate exit of the Wnt signaling protein LRP6 from the endoplasmic reticulum
000133540 269__ $$a2008
000133540 260__ $$c2008
000133540 336__ $$aJournal Articles
000133540 500__ $$aGlobal Health Institute, Faculty of Life Sciences, Ecole Polytechnique Federale de Lausanne, Station 15, CH-1015 Lausanne, Switzerland.
000133540 520__ $$aCanonical Wnt signaling is initiated by binding of Wnt proteins to members of the Frizzled family and subsequent complex formation with lipoprotein receptor-related proteins 5/6 (LRP5/6). Here, we show that LRP6 is palmitoylated on a juxtamembranous cysteine and that palmitoylation is required for exit from the endoplasmic reticulum (ER). We propose that palmitoylation serves to tilt the long, 23-residue transmembrane domain of LRP6 with respect to the plane of membrane to prevent a hydrophobic mismatch and subsequent recognition by the ER quality control. In support of this model, a palmitoylation-deficient LRP6 mutant could be rescued from ER retention by deletion of two to four residues in the transmembrane domain. Importantly, we found that palmitoylation-deficient LRP6 was retained in the ER by a completely novel monoubiquitination-dependent ER retention mechanism. Mutation of a specific lysine indeed abolished ubiquitination of palmitoylation-deficient LRP6 and led to a rescue from ER retention. Finally, at the cell surface, we found that interplay between palmitoylation and ubiquitination was necessary for efficient Wnt signaling.
000133540 700__ $$aAbrami, L.
000133540 700__ $$0240086$$aKunz, B.$$g156390
000133540 700__ $$0242344$$aIacovache, I.$$g172742
000133540 700__ $$0240085$$avan der Goot, F. G.$$g171549
000133540 773__ $$j105$$k14$$q5384-9$$tProc Natl Acad Sci U S A
000133540 909CO $$ooai:infoscience.tind.io:133540$$particle$$pSV
000133540 909C0 $$0252037$$pVDG$$xU11271
000133540 937__ $$aVDG-ARTICLE-2008-010
000133540 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000133540 980__ $$aARTICLE