TY - JOUR
T1 - Coupling the dynamics of two actin networks - New views on the mechanics of cell protrusion
AU - Danuser, G.
PY - 2005/12
Y1 - 2005/12
N2 - We study how mechanical forces integrate spatially and temporally with regulatory signals at the leading edge of migrating cells. To probe the dynamics of this system, we developed quantitative fluorescent speckle microscopy, which maps out actin cytoskeleton transport, assembly and disassembly with high spatial resolution. Statistical processing of single speckle properties revealed two kinetically, kinematically and molecularly distinct, yet spatially overlapping, actin arrays at the leading edge of migrating epithelial cells. The first network, referred to as the lamellipodium, polymerizes and depolymerizes 1-2 μm from the edge in an Arp2/3 (actin-related protein 2/3)- and cofilin-dependent fashion. The second network, referred to as the lamella, exhibits Arp2/3-independent polymerization. To elucidate the dynamic relationship between the two networks, we have begun to examine how assembly and flow are temporally modulated with respect to a protrusion event. In control cells we found bursts of protrusion preceding bursts of F-actin assembly. The time lag disappears in cells where Arp2/3-function is impaired. This and other results allowed us to propose a model in which tropomyosin protects lamella filaments from branching and severing, and to conjecture that Arp2/3-mediated lamellipodium assembly is a natural consequence of lamella expansion, but not the initiator of cell protrusion.
AB - We study how mechanical forces integrate spatially and temporally with regulatory signals at the leading edge of migrating cells. To probe the dynamics of this system, we developed quantitative fluorescent speckle microscopy, which maps out actin cytoskeleton transport, assembly and disassembly with high spatial resolution. Statistical processing of single speckle properties revealed two kinetically, kinematically and molecularly distinct, yet spatially overlapping, actin arrays at the leading edge of migrating epithelial cells. The first network, referred to as the lamellipodium, polymerizes and depolymerizes 1-2 μm from the edge in an Arp2/3 (actin-related protein 2/3)- and cofilin-dependent fashion. The second network, referred to as the lamella, exhibits Arp2/3-independent polymerization. To elucidate the dynamic relationship between the two networks, we have begun to examine how assembly and flow are temporally modulated with respect to a protrusion event. In control cells we found bursts of protrusion preceding bursts of F-actin assembly. The time lag disappears in cells where Arp2/3-function is impaired. This and other results allowed us to propose a model in which tropomyosin protects lamella filaments from branching and severing, and to conjecture that Arp2/3-mediated lamellipodium assembly is a natural consequence of lamella expansion, but not the initiator of cell protrusion.
KW - Actin
KW - Cell protrusion
KW - Epithelial cell
KW - Fluorescent speckle microscopy
KW - Lamella
KW - Lamellipodium
UR - http://www.scopus.com/inward/record.url?scp=28844480915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28844480915&partnerID=8YFLogxK
U2 - 10.1042/BST20051250
DO - 10.1042/BST20051250
M3 - Article
C2 - 16246090
AN - SCOPUS:28844480915
SN - 0300-5127
VL - 33
SP - 1250
EP - 1253
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
IS - 6
ER -