Molecular mechanism of actin-dependent retrograde flow in lamellipodia of motile cells.

In motile, eukaryotic cells, a variety of cell-associated material (collectively termed here as 'particles') continuously flows, relative to the substratum, from the front to the back of the extreme margin of the cell (termed the 'lamellipodium'). This retrograde particle flow, occurs both over the surface of, and inside the lamellipodium. Force to drive retrograde particle flow in lamellipodia is dependent on actin filaments, but the precise mechanism of force generation, and function of the flow is generally not well understood. Actin filaments themselves, in lamellipodia of most motile cell types studied also flow retrograde relative to the substratum. This actin flow, in Aplysia bag cell neuronal growth cones, is known to be driven by activity of a myosin. In these growth cones, retrograde flow of cell surface-attached particles is coupled to retrograde actin flow. In Aplysia, force from retrograde actin flow may limit certain types of growth cone motility. In other motile cell types, such as keratocytes and fibroblasts, the mechanism of retrograde particle flow and function of retrograde actin flow in lamellipodia is poorly understood. For these cell types, recent data provide a basis for proposing alternative actin-based mechanisms to drive retrograde particle flow in lamellipodia. One mechanism is based on activity of a putative pointed end- directed actin motor, and the other on tension-driven surface lipid flow. Here I will review recent advances that have been made in determining the molecular mechanism of force generation to drive retrograde particle flow relative to the substratum in lamellipodia of motile cells. I will address the function of retrograde actin flow in lamellipodia, and apparent differences between Aplysia and other motile cell types.

[1]  S. Mann,et al.  Ciba Foundation Symposium , 1997 .

[2]  M. Sheetz,et al.  Axon membrane flows from the growth cone to the cell body , 1995, Cell.

[3]  M. Bretscher.  Directed lipid flow in cell membranes , 1976, Nature.

[4]  N. Hirokawa,et al.  Incorporation and turnover of biotin-labeled actin microinjected into fibroblastic cells: an immunoelectron microscopic study , 1989, The Journal of cell biology.

[5]  P. Bridgman,et al.  Nerve growth cone lamellipodia contain two populations of actin filaments that differ in organization and polarity , 1992, The Journal of cell biology.

[6]  J. Small,et al.  Actin filament organization in the fish keratocyte lamellipodium , 1995, The Journal of cell biology.

[7]  T. Mitchison,et al.  Comparison of actin and cell surface dynamics in motile fibroblasts , 1992, The Journal of cell biology.

[8]  T. Mitchison,et al.  Actin-Based Cell Motility and Cell Locomotion , 1996, Cell.

[9]  James A. Spudich,et al.  Capping of surface receptors and concomitant cortical tension are generated by conventional myosin , 1989, Nature.

[10]  M. Kirschner,et al.  Cytoskeletal dynamics and nerve growth , 1988, Neuron.

[11]  K. Jacobson,et al.  The direction of membrane lipid flow in locomoting polymorphonuclear leukocytes. , 1990, Science.

[12]  J. Heath,et al.  Cell locomotion: new research tests old ideas on membrane and cytoskeletal flow. , 1991, Cell motility and the cytoskeleton.

[13]  D. Bray,et al.  Model for Membrane Movements in the Neural Growth Cone , 1973, Nature.

[14]  J. Heath,et al.  On the mechanisms of cortical actin flow and its role in cytoskeletal organisation of fibroblasts. , 1993, Symposia of the Society for Experimental Biology.

[15]  A. Bershadsky,et al.  Actin cytoskeleton of spread fibroblasts appears to assemble at the cell edges. , 1986, Journal of cell science.

[16]  J. Hammer,et al.  Subcellular localization of myosin V in nerve growth cones and outgrowth from dilute-lethal neurons , 1997 .

[17]  E. Elson,et al.  Cell migration does not produce membrane flow , 1990, The Journal of cell biology.

[18]  J. Wolenski,et al.  Function of Myosin-V in Filopodial Extension of Neuronal Growth Cones , 1996, Science.

[19]  T. Mitchison,et al.  Investigation of the mechanism of retraction of the cell margin and rearward flow of nodules during mitotic cell rounding. , 1997, Molecular biology of the cell.

[20]  T. Svitkina,et al.  Myosin II filament assemblies in the active lamella of fibroblasts: their morphogenesis and role in the formation of actin filament bundles , 1995, The Journal of cell biology.

[21]  A. Harris,et al.  Centripetal transport of attached particles on both surfaces of moving fibroblasts. , 1972, Experimental cell research.

[22]  R Nuydens,et al.  Lateral diffusion and retrograde movements of individual cell surface components on single motile cells observed with Nanovid microscopy , 1991, The Journal of cell biology.

[23]  H. Goodson,et al.  Motors and membrane traffic. , 1997, Current opinion in cell biology.

[24]  J. Dai,et al.  Mechanical properties of neuronal growth cone membranes studied by tether formation with laser optical tweezers. , 1995, Biophysical journal.

[25]  Julie A. Theriot,et al.  Actin microfilament dynamics in locomoting cells , 1991, Nature.

[26]  S. J. Smith,et al.  Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone , 1988, The Journal of cell biology.

[27]  A K Harris,et al.  Locomotion of tissue culture cells considered in relation to ameboid locomotion. , 1994, International review of cytology.

[28]  G. Oster,et al.  The physics of lamellipodial protrusion , 1996, European Biophysics Journal.

[29]  E. Bonder,et al.  Identification of coelomocyte unconventional myosin and its association with in vivo particle/vesicle motility. , 1994, Journal of cell science.

[30]  E. Elson,et al.  Surface particle transport mechanism independent of myosin II in Dictyostelium , 1992, Nature.

[31]  Andrzej GręObecki,et al.  Membrane and Cytoskeleton Flow in Motile Cells with Emphasis on the Contribution of Free-Living Amoebae , 1994 .

[32]  E. Elson,et al.  Forward transport of glycoproteins on leading lamellipodia in locomoting cells , 1989, Nature.

[33]  Heath Jp,et al.  On the mechanisms of cortical actin flow and its role in cytoskeletal organisation of fibroblasts. , 1993 .

[34]  D. Soll,et al.  In Ascaris sperm pseudopods, MSP fibers move proximally at a constant rate regardless of the forward rate of cellular translocation. , 1995, Cell motility and the cytoskeleton.

[35]  Hong Qian,et al.  Nanometre-level analysis demonstrates that lipid flow does not drive membrane glycoprotein movements , 1989, Nature.

[36]  P. Forscher,et al.  Growth cone advance is inversely proportional to retrograde F-actin flow , 1995, Neuron.

[37]  T. Mitchison,et al.  Myosin is involved in postmitotic cell spreading , 1995, The Journal of cell biology.

[38]  T. Mitchison,et al.  Control of actin polymerization in live and permeabilized fibroblasts , 1991, The Journal of cell biology.

[39]  M. Sheetz,et al.  Glycoprotein motility and dynamic domains in fluid plasma membranes. , 1993, Annual review of biophysics and biomolecular structure.

[40]  D A Lauffenburger,et al.  Simulation of integrin-cytoskeletal interactions in migrating fibroblasts. , 1994, Biophysical journal.

[41]  N. Hirokawa,et al.  Actin dynamics in growth cones , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  M. Sheetz,et al.  Concentration of membrane antigens by forward transport and trapping in neuronal growth cones , 1990, Cell.

[43]  H. Huxley,et al.  Muscular Contraction and Cell Motility , 1973, Nature.

[44]  P. Forscher,et al.  Myosin drives retrograde F-actin flow in neuronal growth cones. , 1997, Neuron.

[45]  S. Singer,et al.  The fluid mosaic model of the structure of cell membranes. , 1972, Science.

[46]  Y. Wang,et al.  Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling , 1985, The Journal of cell biology.

[47]  H. Higuchi,et al.  Butanedione monoxime suppresses contraction and ATPase activity of rabbit skeletal muscle. , 1989, Journal of biochemistry.

[48]  D. Taylor,et al.  Centripetal transport of cytoplasm, actin, and the cell surface in lamellipodia of fibroblasts. , 1988, Cell motility and the cytoskeleton.

[49]  J. Small,et al.  Polarity of actin at the leading edge of cultured cells , 1978, Nature.

[50]  J. Spudich,et al.  Structure and function of the cytoskeleton of a Dictyostelium myosin- defective mutant , 1990, The Journal of cell biology.

[51]  D. Helbing,et al.  The upright position of brush border-type microvilli depends on myosin filaments. , 1992, Journal of cell science.

[52]  A. Harris.  Cell surface movements related to cell locomotion. , 1973, Ciba Foundation symposium.

[53]  Timothy J. Mitchison,et al.  Identification of Novel Graded Polarity Actin Filament Bundles in Locomoting Heart Fibroblasts: Implications for the Generation of Motile Force , 1997, The Journal of cell biology.

[54]  G. Borisy,et al.  Non-sarcomeric mode of myosin II organization in the fibroblast lamellum , 1993, The Journal of cell biology.

[55]  M. Bretscher.  Moving Membrane up to the Front of Migrating Cells , 1996, Cell.