Nocodazole, vinblastine and taxol at low concentrations affect fibroblast locomotion and saltatory movements of organelles.
Microtubules (MTs) are essential for the maintenance of asymmetric cell shape and motility of fibroblasts. MTs are considered to function as rails for organelle transport to the leading edge. We investigated the relationship between the motility of Vero fibroblasts and saltatory movements of particles in their lamella Fibroblasts extended their leading edges into the experimental wound at a rate of 20+/-11 microm/h. Intracellular particles in the front parts of the polarized fibroblasts moved saltatorily mainly along the long axis of the cells. MT depolymerization induced by the nocodazole at a high concentration (1.7 microM) resulted in the inhibition of both fibroblast motility and saltatory movements of the particles. Taxol (1 microM) inhibited the fibroblast locomotion but not the saltatory movements. The saltatory movement pattern was disorganized by taxol by decreasing the portion of longitudinal saltations and consequently by increasing the part of saltations perpendicular to the cell long axis. This effect may be explained by disorganization of the MT network resulting from the inhibition of dynamic instability. To further investigate the relationships between the MT dynamics instability, saltatory movements, and fibroblast locomotion, we treated fibroblasts with microtubule drugs at low concentration (nocodazole, 170 nM; vinblastine, 50 nM; and taxol, 50 nM). All these drugs induced rapid disorganization of the saltatory movements and decreased the rate of cell locomotion. Simultaneously, the amount of acetylated (stable) MTs increased. The treatment also induced reversible changes in the actin meshwork. We suggest that decrease in the fibroblast locomotion rate in the case of MT stabilization occurred because of the appearance of numerous free MTs. Saltations along free MTs are poorly organized and, as a result, the number of organelles reaching the fibroblast leading edge decreases.
Grigoriev
I S
IS
Laboratory of Cell Motility, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia. ilya08@yahoo.com
Chernobelskaya
A A
AA
Vorobjev
I A
IA
D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D008870:Microtubules / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology*; D015388:Organelles / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D014709:Vero Cells; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine; D017239:Paclitaxel; D015739:Nocodazole