TY - JOUR
T1 - Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion
AU - Totsukawa, Go
AU - Matsuo, Ayaka
AU - Kubota, Ayano
AU - Taguchi, Yuya
AU - Kondo, Hisao
N1 - Funding Information:
We would like to thank H.A. Popiel for her kind assistance in preparation of the manuscript. This work is supported by a grant to H.K. from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Project No. 24370082 ); and the Daiichi-Sankyo Foundation of Life Sciences .
PY - 2013/4
Y1 - 2013/4
N2 - Highlights: VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2.Phosphorylated VCIP135 does not bind to p97ATPase. The phosphorylation of VCIP135 inhibits p97ATPase-mediated Golgi membrane fusion. In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.
AB - Highlights: VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2.Phosphorylated VCIP135 does not bind to p97ATPase. The phosphorylation of VCIP135 inhibits p97ATPase-mediated Golgi membrane fusion. In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.
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U2 - 10.1016/j.bbrc.2013.02.090
DO - 10.1016/j.bbrc.2013.02.090
M3 - Article
C2 - 23500464
AN - SCOPUS:84877662802
SN - 0006-291X
VL - 433
SP - 237
EP - 242
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -