The thrombin receptor (PAR1) is associated with microtubules, mitosis and process formation in glioma cells
Valery Golderman,
Shany Guly Gofrit,
Yanina Ivashko-Pachima,
Illana Gozes,
Joab Chapman,
Efrat Shavit-Stein
Affiliations
Valery Golderman
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; Department of Neurology and Neurosurgery, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv, 6997801, Israel
Shany Guly Gofrit
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, 52621, Israel
Yanina Ivashko-Pachima
Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences, Adams Super Center for Brain Studies and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 6997801, Israel
Illana Gozes
Elton Laboratory for Molecular Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Faculty of Medical and Health Sciences, Adams Super Center for Brain Studies and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 6997801, Israel
Joab Chapman
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; Department of Neurology and Neurosurgery, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv, 6997801, Israel; Robert and Martha Harden Chair in Mental and Neurological Diseases, Faculty of Medical and Health Sciences, Tel Aviv University, 6997801, Israel
Efrat Shavit-Stein
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; Department of Neurology and Neurosurgery, Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv, 6997801, Israel; The TELEM Rubin Excellence in Biomedical Research Program, The Chaim Sheba Medical Center, Ramat Gan, 52621, Israel; Corresponding author.Department of Neurology, The Chaim Sheba Medical Center, Ramat-Gan 52621, Israel.
The cell surface protease-activated receptor 1 (PAR1) is overexpressed in glioblastoma multiforme (GBM). We studied the function and structure of intracellular microtubule (MT) and PAR1 in a tubulin-mediated process. We found that exposure to thrombin increased the percentage of proliferative, S, and M phases cells, affected morphology, and increased process elongation. PAR1 antagonist inversely affects these measures, increases tubulin end-binding protein 3 (EB3) mRNA expression in C6 cells, and reduces EB3 comet length, track length, and duration in neuroblastoma cells. In addition, immunofluorescence staining suggests that PAR1 is in close association with the MT α-tubulin and with coagulation cascade proteins during cell division stages. Our findings support PAR1 involvement in MT dynamics.
