Coordination of molecular motors: from in vitro assays to intracellular dynamics

Abstract

New technologies have emerged that enable the tracking of molecular motors and their cargos with very high resolution both in vitro and in live cells. Classic in vitro motility assays are being supplemented with assays of increasing complexity that more closely model the cellular environment. In cells, the introduction of probes such as quantum dots allows the high-resolution tracking of both motors and vesicular cargos. The 'bottom up' enhancement of in vitro assays and the 'top down' analysis of motility inside cells are likely to converge over the next few years. Together, these studies are providing new insights into the coordination of motors during intracellular transport.

Figure 1. Multiple motor proteins, including dynein, kinesin, and myosin-V, drive vesicle motility along the complex cellular cytoskeleton

In this electron micrograph showing a platinum replica of an unroofed rat embryonic fibroblast, a vesicle pseudo-colored in yellow is bound along a microtubule (green), in the vicinity of an actin filament highlighted in red. Schematic structures of the motors dynein (D), kinesin (K), and myosin-V (M) are drawn approximately to scale. The authors gratefully acknowledge Tatyana Svitkina of the University of Pennsylvania for providing the electron micrograph.

Figure 2. Mechanisms for interaction between the motor components

A, a double-headed motor, such as myosin V is bound to its track, actin (red), by both heads. The trailing head (blue) detaches and steps forward (A → B) to become the leading head. Due to stretch of the molecule required to reach the next binding site, the leading head is pulled backward (blue arrow in B) and the trailing head is pulled forward (green arrow in B). C and D, two myosin V molecules bound to the same cargo particle and to the same actin filament. When one of the motors (green) steps forward (C → D), the cargo moves half as far as the motor steps. Attachment and motor compliances strain the stepping motor backwards and the non-stepping motor (blue) forward (arrows in D). E, an extra regulatory component (blue arrow) may control the activity of the motors. F, a filament binding protein, such as tropomyosin (light blue arrow) drawn here or MAPs, might regulate motor-track interactions and cooperative behavior of nearby motors.

Box Figure 1