Louise P. Cramer

The Randall Institute, Kings College London, 26-29 Drury Lane, London WC2B 5RL, UK.

Received 5/21/97; Accepted 5/26/97

6. PERSPECTIVE

I have described a number of actin-dependent motile forces to drive retrograde particle flow and actin flow relative to the substratum in lamellipodia. The prevalent mechanism in which all retrograde flow of particles reflect coupling to moving actin filaments needs to be tested more rigorously in different motile cell types. To solve this issue, and those of function, taking advantage of known motile systems that are defective in specific myosins, and developing better myosin inhibitors is needed. Also required is the ability to detect markers of actin filaments, a variety of different particles, and lipids at better resolution. This may require development of new markers. For example, are there actin filaments in lamellipodia whose dynamic behavior is yet undetected by current methods? Also, it is a distinct possibility that more than one mechanism operates in the same lamellipodium. For example, some particles (either internal or cell surface-attached) could be coupled to actin flow, independent of distinct cell surface-attached particles coupled to lipid flow. Similarly, if all actin filaments are stationary in lamellipodia, retrograde flow of internal particles may be driven indepedently to retrograde flow of distinct particles on the cell surface.

Another direction for the future is to determine how retrograde flow relative to the substratum in lamellipodia is coordinated with that in the lamella and cell body of the same motile cell. For example it is clear that in Aplysia growth cones and amoeba cells, certain individual particles can traverse, relative to the substratum, both the lamellipodium and lamella (3, 26). In amoeba, this can continue, relative to the substratum, across the cell body (3). How does this occur? In Aplysia growth cones, the data are more consistent with a single type of force continuously transporting the same particle. In amoeba, the data are less clear, and instead distinct forces may differentially contribute to transporting the same particle in different regions of the same cell (e.g. as can occur for motor-driven intracellular vesicle transport).