Cell motility and microtubules in cultured fibroblasts from patients with Kartagener syndrome.
Patients with Kartagener syndrome (KS) show defects in ciliary and flagellar movement that are usually associated with the partial or total absence of dynein side arms from axonemal microtubules. Dynein is essential for such movements, but its involvement in other cellular (particularly microtubule-related) processes is unknown. It has recently been reported that neutrophils from KS patients show impaired motility including responses to chemotactic stimuli, suggesting that dynein-like proteins may be generally involved in motile processes. In support of this, we have now found that spontaneous motility of cultured skin fibroblasts from KS patients is also markedly impaired. Three cell lines derived from skin explants of KS patients with deficient dynein side arms in nasal cilia and eight cell lines derived from normal volunteers were studied. Fibroblasts were seeded into dishes containing colloidal gold-coated cover glasses [Albrecht-Buehler, 1977], incubated for 24h at 37 degrees C, and the area of cell "phagokinetic" tracks determined. Each cell line studied in this manner reproducibly displayed an amount of spontaneous motility characteristic for that cell line. The mean track area (+/- SE) for all control cells studied was 14.6 +/- 0.5 X 10(3) micron2 whereas for KS fibroblasts was 8.7 +/- 0.4 X 10(3) micron2 (P less than 0.001). Immunofluorescence microscopy using antitubulin and antihuman 210 K MAP antibodies revealed no differences in the staining patterns between control and KS fibroblasts. Pinocytic rates were identical, and the complement of tubulin and major microtubule associated proteins as seen on one-dimensional SDS polyacrylamide gel autoradiographs appeared similar for control and KS cells. Thus, the observed motility defect is probably not the result of alterations in the occurrence or distribution of microtubules or in the occurrence or binding of the major microtubule-associated proteins. This defect in cellular motility may be related to the absence of dynein or may reflect another independent cellular defect.
D000251:Adenosine Triphosphatases / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D004398:Dyneins / Q000502:physiology*; D006801:Humans; D007619:Kartagener Syndrome / Q000503:physiopathology*; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000502:physiology*; D010587:Phagocytosis; D010873:Pinocytosis; D011485:Protein Binding; D011506:Proteins / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D011506:Proteins; D014404:Tubulin; D000251:Adenosine Triphosphatases; D004398:Dyneins