Dynein regulates cell migration depending on substrate rigidity.
The mechanical environment in combination with biochemical signaling is             an important regulatory factor for cellular physiology including tissue development,             cell motility and differentiation. Exerting a tractional force triggered by myosin-dependent             cell contractility is known to be an indispensible element of cell migration in             a mechanically stiff environment such as a 2D planar surface. However, a number             of reports have argued that the requirement of myosin activity for cell migration             is limited by cell type and the environment. In this study, we present evidence             that dynein, a minus end-directed microtubule motor, plays a central role in cell             migration in the absence of tractional force. Interfering with the dynein activity             through a dynein-specific inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA),             dramatically inhibited 2D migration of the fibroblast when cell contractility             was blocked by Rho kinase or a myosin inhibitor, although EHNA itself did not             affect cell migration. Cell migration in 3D soft collagen matrices, where the             cell exerts a relatively low tractional force compared to that on a 2D stiff surface,             is also profoundly inhibited by dynein intermediate chain (DIC) silencing regardless             of the presence of myosin activity. In addition, DIC-silenced cells on a soft             acrylamide surface show decreased migration without blockade of myosin activity.             Taken together, our results suggest that dynein may be a primary regulatory factor             for cell migration when a cell is in a mechanically low-tension environment, such             as in a 3D matrix.
School of Biological Sciences (BK21 Program), Chung-Ang University,                     Seoul 156-756, Republic of Korea.
Daehwan
D
Kim
Eunae
E
You
Sangmyung
S
Rhee
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D009218:Myosins / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D054460:rho-Associated Kinases; D009218:Myosins; D004398:Dyneins