TY - JOUR
T1 - Cell migration without a lamellipodium
T2 - Translation of actin dynamics into cell movement mediated by tropomyosin
AU - Gupton, Stephanie L.
AU - Anderson, Karen L.
AU - Kole, Thomas P.
AU - Fischer, Robert S.
AU - Ponti, Aaron
AU - Hitchcock-DeGregori, Sarah E.
AU - Danuser, Gaudenz
AU - Fowler, Velia M.
AU - Wirtz, Denis
AU - Hanein, Dorit
AU - Waterman-Storer, Clare M.
PY - 2005/2/14
Y1 - 2005/2/14
N2 - The actin cytoskeleton is locally regulated for functional specializations for cell motility. Using quantitative fluorescent speckle microscopy (qFSM) of migrating epithelial cells, we previously defined two distinct F-actin networks based on their F-actin-binding proteins and distinct patterns of F-actin turnover and movement. The lamellipodium consists of a treadmilling F-actin array with rapid polymerization-dependent retrograde flow and contains high concentrations of Arp2/3 and ADF/cofilin, whereas the lamella exhibits spatially random punctae of F-actin assembly and disassembly with slow myosin-mediated retrograde flow and contains myosin II and tropomyosin (TM). In this paper, we micro-injected skeletal muscle α TM into epithelial cells, and using qFSM, electron microscopy, and immunolocalization show that this inhibits functional lamellipodium formation. Cells with inhibited lamellipodia exhibit persistent leading edge protrusion and rapid cell migration. Inhibition of endogenous long TM isoforms alters protrusion persistence. Thus, cells can migrate with inhibited lamellipodia, and we suggest that TM is a major regulator of F-actin functional specialization in migrating cells.
AB - The actin cytoskeleton is locally regulated for functional specializations for cell motility. Using quantitative fluorescent speckle microscopy (qFSM) of migrating epithelial cells, we previously defined two distinct F-actin networks based on their F-actin-binding proteins and distinct patterns of F-actin turnover and movement. The lamellipodium consists of a treadmilling F-actin array with rapid polymerization-dependent retrograde flow and contains high concentrations of Arp2/3 and ADF/cofilin, whereas the lamella exhibits spatially random punctae of F-actin assembly and disassembly with slow myosin-mediated retrograde flow and contains myosin II and tropomyosin (TM). In this paper, we micro-injected skeletal muscle α TM into epithelial cells, and using qFSM, electron microscopy, and immunolocalization show that this inhibits functional lamellipodium formation. Cells with inhibited lamellipodia exhibit persistent leading edge protrusion and rapid cell migration. Inhibition of endogenous long TM isoforms alters protrusion persistence. Thus, cells can migrate with inhibited lamellipodia, and we suggest that TM is a major regulator of F-actin functional specialization in migrating cells.
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U2 - 10.1083/jcb.200406063
DO - 10.1083/jcb.200406063
M3 - Article
C2 - 15716379
AN - SCOPUS:13944273671
SN - 0021-9525
VL - 168
SP - 619
EP - 631
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -