A role for tumor protein TPD52 phosphorylation in endo-membrane trafficking during cytokinesis
- University of Wisconsin, Department of Nutritional Sciences 1415 Linden Dr., Madison, WI 53706 (United States)
- University of Wisconsin, Medical School Electron Microscope Facility, 1300 University Ave, Madison, WI 53706 (United States)
Research highlights: {yields} D52 localizes to vesicles at the mid-line in multinucleated cells. {yields} Expression of a D52 serine136/alanine mutant induced multinucleation of cells. {yields} D52 localizes to VAMP 8 positive endosomes necessary for cytokinesis. {yields} The Ca{sup 2+}-dependent phosphorylation of D52 regulates cytokinesis. -- Abstract: Tumor protein D52 is expressed at high levels in exocrine cells containing large secretory granules where it regulates Ca{sup 2+}-dependent protein secretion; however, D52 expression is also highly induced in multiple cancers. The present study investigated a role for the Ca{sup 2+}-dependent phosphorylation of D52 at the single major phospho-acceptor site serine 136 on cell division. Ectopic expression of wild type D52 (D52wt) and the phosphomutants serine 136/alanine (S136A) or serine 136/glutamate (S136/E) resulted in significant multinucleation of cells. D52wt and S136/E each resulted in a greater than 2-fold increase in multinucleated cells compared to plasmid-transfected controls whereas the S136/A phospho-null mutant caused a 9-fold increase in multinucleation at 48 h post-transfection. Electron microscopy revealed D52 expression induced a marked accumulation of vesicles along the mid-line between nuclei where the final stages of cell abscission normally occurs. Supporting this, D52wt strongly colocalized on vesicular structures containing the endosomal regulatory protein vesicle associated membrane protein 8 (VAMP 8) and this colocalization significantly increased with elevations in cellular Ca{sup 2+}. As VAMP 8 is known to be necessary for the endo-membrane fusion reactions that mediate the final stages of cytokinesis, these data indicate that D52 expression and phosphorylation at serine 136 play an important role in supporting the Ca{sup 2+}-dependent membrane trafficking events necessary for cytokinesis in rapidly proliferating cancer cells.
- OSTI ID:
- 22202900
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 402, Issue 4; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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