ISSN 0006-3509, Biophysics, 2010, Vol. 55, No. 6, pp. 916–920. © Pleiades Publishing, Inc., 2010.
Original Russian Text © A.V. Burakov, E.S. Nadezhdina, 2010, published in Biofizika, 2010, Vol. 55, No. 6, pp. 996–1001.
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INTRODUCTION
Migration of animal cells, or locomotion, is one of
paramount processes, playing a definitive role in
development and further vital activity of the multicel-
lular organism. During embryo development, orga-
nized cell movement in a definite direction takes place
already in the course of gastrulation and then during
formation of the neural fold and neuraxis. In the adult
individual, cell locomotion provides for development
of the immune response (cell migration into the
inflammatory focus, neutrophil rolling and penetra-
tion through the vessel wall). Cell migration takes
place during wound healing, in particular, skin injury
evokes fibroblast migration into the wound zone; it
also happens during remodeling of the blood vessel
and myocardium and during development of athero-
sclerosis (plaque formation). Cell locomotion plays an
important part in carcinogenesis, providing for tumor
invasion into surrounding tissue and penetration of
single tumor cells into lymph or blood vessels at the
stage of metastasis.
The main role in cell locomotion belongs to the
actomyosin component of the cytoskeleton. However,
even the early works devoted to a study of cell motility
noted the participation of microtubules in this process
[1–3]. Some cells of moderate size, such as fish kera-
tocytes or leukocytes, are capable of locomotion at the
sole expense of their actomyosin system even after
experimental destruction of microtubules [4, 5]. How-
ever, the larger fibroblasts after destruction of microtu-
bules are capable only of chaotic pseudopodial activity
but not of directional movement [1–3]. The role of
Editor’s Note: I certify that this text exactly reproduces all factual
statements and closely conveys the phrasing and style of the
original Russian publication. A.G.
microtubules in cell locomotion still remains obscure.
It is supposed that microtubules serve as “rails” in the
transport of various cell components required for
motion to the anterior edge of the cell. The system of
dynamic microtubules 25 nm in diameter, consisting
of tubulin dimers, in most of animal cells is organized
in the form of a radially symmetric star with rays
spreading from the cell center to the periphery. Such
organization of the tubulin cytoskeleton is optimally
adapted for efficient intracellular transport with the
aid of motor proteins, specifically binding with various
cargoes and directionally transferring them to proper
cell compartments. It has been shown that the drop in
the rate of migration of a fibroblast is proportional to
the decrease in the amount of its microtubules during
their gradual disassembly in the presence of nanomo-
lar doses of nocodazole [6, 7]. Again, stabilization of
microtubules leads to a decrease in cell motility. It has
also been shown that microtubules in a moving cell are
polarized along the axis of cell movement so that their
dynamic plus-ends face the leading edge of the cell,
while the centrosome is positioned, as a rule, between
the nucleus and the leading edge [8, 9]. This appar-
ently determines the direction of membrane transport
to the leading edge of the fibroblast, which favors for-
mation of new membrane in this place and sets the
direction of further cell movement. However, the role
of ordered disposition of microtubules also remains
obscure.
Mammalian fibroblast-like cells owing to their
ability of directed locomotion are often used in works
devoted to the study of cell motility. Such cells of var-
ious lines usually possess a well-organized radially
symmetric system of microtubules. The use of chemi-
cals to decrease the ability of such cells to move, as a
rule, leads either to disassembly of microtubules
MOLECULAR BIOPHYSICS
Protein Kinase LOSK Regulates the Network
of Microtubules and Cell Locomotion
A. V. Burakov
a
and E. S. Nadezhdina
b
a
Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119991 Russia
b
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia
Received August 27, 2010
Abstract—It has been found that inhibition of the activity of protein kinase LOSK reduces the ability of cells
to perform directed movement over the substrate and changes the parameters of interaction of cells with the
substrate. It is suggested that chaotization of microtubules leads to stabilization of cell contacts with the sub-
strate and, consequently, to slowdown of locomotion.
Keywords: microtubules, locomotion, cell contacts, wound monolayer
DOI: 10.1134/S0006350910060059