Localization of Ca(2+)-calmodulin to the kinetochore of C6 glioma cells: an investigation of the anti-tumour effects of calmodulin antagonists in the treatment of brain tumours.
As part of our research on the anti-tumour effects of calmodulin antagonists, we examined the localization of Ca(2+)-calmodulin in mitotic C6 glioma cells. Monoclonal anticalmodulin antibodies which require Ca2+ for binding and CREST serum which recognizes kinetochores were used to stain ultrathin frozen sections. By indirect immunofluorescence and immunoelectron microscopy of colcemid-treated cells, Ca(2+)-calmodulin was present in the kinetochore region of the cell. By double label indirect immunofluorescence using anticalmodulin antibodies and CREST serum to stain untreated cells, calmodulin was found to colocalize with kinetochores. On the basis of these results, we hypothesize that Ca(2+)-calmodulin in the kinetochore depolymerizes the microtubules which are transported by dynein in the kinetochore during metaphase oscillating and anaphase poleward chromosomal movements. This hypothesis, which is currently under further investigation, may help explain a mechanism for the antitumour effects of calmodulin antagonists in the treatment of brain tumours.
Mitsuyama
F
F
Department of Neurosurgery, Fujita Health University, Aichi, Japan.
Kanno
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000648:ultrastructure; D002118:Calcium / Q000032:analysis*; D002147:Calmodulin / Q000032:analysis* / Q000037:antagonists & inhibitors; D003703:Demecolcine; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000737:chemistry* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D051381:Rats; D008941:Spindle Apparatus / Q000737:chemistry
D000970:Antineoplastic Agents; D002147:Calmodulin; D002118:Calcium; D003703:Demecolcine