The impairment of the assembly of vimentin filaments leads to suppression of the formation and maturation of focal contacts and an alteration of the type of cellular protrusions

Author:

Zholudeva A. O.1,Potapov N. S.2,Kozlova E. A.2,Lomakina M. E.1,Alexandrova A. Y.1

Affiliation:

1. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

2. Lomonosov Moscow State University

Abstract

Cell migration is largely determined by the type of protrusions formed by the cell. Mesenchymal migration is accomplished by the formation of lamellipodia and/or filopodia, and membrane blebs lay at the basis of amoeboid migration. Changing the conditions of migration can lead to an alteration of the character of cell movement, for example, inhibition of Arp2/3-dependent actin polymerization by the CK-666 inhibitor leads to transition from mesenchymal to amoeboid motility type. The ability of cells to switch from one type of motility to another is called migration plasticity. The cellular mechanisms regulating migratory plasticity are poorly understood. One of the factors determining the possibility of migratory plasticity may be the presence and/or organization of vimentin intermediate filaments (VIFs). To investigate whether the organization of the VIF network affects the ability of fibroblasts to form membrane blebs, we used rat embryonic fibroblasts REF52 with normal VIF organization, with VIF knockout (REF–/–) and with a mutation inhibiting the assembly of full-length VIFs (REF117). Blebs formation was induced by treatment of cells with CK-666. Vimentin knockout did not lead to statistically significant increase of number of cells with blebs. In fibroblasts with short fragments of vimentin the number of cells forming blebs both spontaneously and in presence of CK-666 increased significantly. Disruption of the VIF organization did not lead to the significant changes in microtubules network or myosin light chain phosphorylation, but caused a significant reduction of the focal contact system. The most pronounced and statistically significant decrease in both the size and number of focal adhesions were observed in REF117. We believe that the regulation of membrane blebbing by VIFs is mediated by their effect on the focal adhesion system. Analysis of migration of fibroblasts with different organization of VIFs in a three-dimensional collagen gel showed that the organization of VIFs determines the type of cell protrusions, which in turn determines the character of cell movement. A novel role of VIF as a regulator of membrane blebbing, essential for the manifestation of migratory plasticity, is shown.

Publisher

The Russian Academy of Sciences

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