{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:15:22Z","timestamp":1791238522642,"version":"4.1.0"},"reference-count":65,"publisher":"American Society for Cell Biology (ASCB)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:p>Gaucher disease is a lysosomal storage disorder caused by a defect in the degradation of glucosylceramide catalyzed by the lysosomal enzyme \u03b2-glucocerebrosidase (GBA). GBA reaches lysosomes via association with its receptor, lysosomal integral membrane protein type 2 (LIMP-2). We found that distinct phosphatidylinositol 4-kinases (PI4Ks) play important roles at multiple steps in the trafficking pathway of the LIMP-2\/GBA complex. Acute depletion of phosphatidylinositol 4-phosphate in the Golgi caused accumulation of LIMP-2 in this compartment, and PI4KIII\u03b2 was found to be responsible for controlling the exit of LIMP-2 from the Golgi. In contrast, depletion of PI4KII\u03b1 blocked trafficking at a post-Golgi compartment, leading to accumulation of LIMP-2 in enlarged endosomal vesicles. PI4KII\u03b1 depletion also caused secretion of missorted GBA into the medium, which was attenuated by limiting LIMP-2\/GBA exit from the Golgi by PI4KIII\u03b2 inhibitors. These studies identified PI4KIII\u03b2 and PI4KII\u03b1 as important regulators of lysosomal delivery of GBA, revealing a new element of control to sphingolipid homeostasis by phosphoinositides.<\/jats:p>","DOI":"10.1091\/mbc.e11-06-0553","type":"journal-article","created":{"date-parts":[[2012,2,16]],"date-time":"2012-02-16T07:53:14Z","timestamp":1329378794000},"page":"1533-1545","source":"Crossref","is-referenced-by-count":100,"title":["Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, \u03b2-glucocerebrosidase"],"prefix":"10.1091","volume":"23","author":[{"given":"Marko","family":"Jovi\u0107","sequence":"first","affiliation":[{"name":"Section on Molecular Signal Transduction, Program for Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle 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