Golgi-associated GSK3beta regulates the sorting process of post-Golgi membrane trafficking.
Glycogen synthase kinase β (GSK3β) phosphorylates many substrates in mammalian cells, and functions in many physiological processes. We observed that GSK3β knockdown by siRNA perturbed both Golgi morphology in HeLa cells and the anterograde transport of cation-independent mannose 6-phosphate receptor (CI-M6PR) from the trans-Golgi network (TGN) to prelysosomal compartments (PLC), diverting it to the exocytic pathway. Moreover, we demonstrate that a portion of GSK3β was localized to the TGN through the Golgi peripheral protein p230 and that this localization regulated CLASP2 phosphorylation. Our results also show that GSK3β knockdown resulted in accumulation of CLASP2 at microtubule plus ends at the cell periphery. Our findings support the hypothesis that GSK3β at the TGN acts as a guide, activates exocytic transport, and redirects CI-M6PR from transport to the PLC into the exocytic pathway by regulating the affinity of CLASPs for microtubules.
Adachi
Atsuhiro
A
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan.
Kano
Fumi
F
Tsuboi
Takashi
T
Fujita
Morihisa
M
Maeda
Yusuke
Y
Murata
Masayuki
M
D001324:Autoantigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005089:Exocytosis / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000378:metabolism*
D001324:Autoantigens; C497851:CLASP2 protein, human; C098772:GOLGA4 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3