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Vol. 11, Issue 7, 2201-2211, July 2000

Accumulation of rab4GTP in the Cytoplasm and Association with the Peptidyl-Prolyl Isomerase Pin1 during Mitosis

Lisya Gerez,* Karin Mohrmann,* Marcel van Raak,* Mandy Jongeneelen,* Xiao Zhen Zhou,dagger Kun Ping Lu,dagger and Peter van der Sluijs*Dagger

 *Department of Cell Biology and Institute of Biomembranes, Utrecht University Medical Center, 3584 CX Utrecht, The Netherlands, and  dagger Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, and Division on Aging, Harvard Medical School, Boston, Massachusetts 02215

Transport through the endocytic pathway is inhibited during mitosis. The mechanism responsible for this inhibition is not understood. Rab4 might be one of the proteins involved as it regulates transport through early endosomes, is phosphorylated by p34cdc2 kinase, and is translocated from early endosomes to the cytoplasm during mitosis. We investigated the perturbation of the rab4 GTPase cycle during mitosis. Newly synthesized rab4 was less efficiently targeted to membranes during mitosis. By subcellular fractionation of mitotic cells, we found a large increase of cytosolic rab4 in the active GTP-form, an increase not associated with the cytosolic rabGDP chaperone GDI. Instead, phosphorylated rab4 is in a complex with the peptidyl-prolyl isomerase Pin1 during mitosis, but not during interphase. Our results show that less efficient recruitment of rab4 to membranes and a bypass of the normal GDI-mediated retrieval of rab4GDP from early endosomes reduce the amount of rab4GTP on membranes during mitosis. We propose that phosphorylation of rab4 inhibits both the recruitment of rab4 effector proteins to early endosomes and the docking of rab4-containing transport vesicles. This mechanism might contribute to the inhibition of endocytic membrane transport during mitosis.


Dagger Corresponding author. E-mail address: pvander{at}knoware.nl.


Molecular Biology of the Cell
Vol. 11, 2201-2211, July 2000
Copyright © 2000 by The American Society for Cell Biology



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