Dynamic catch-bonding generates the large stall forces of cytoplasmic dynein

Abstract

Cytoplasmic dynein is an important molecular motor involved in the transport of vesicular and macromolecular cargo along microtubules in cells, often in conjunction with kinesin motors. Dynein is larger and more complex than kinesin and the mechanism and regulation of its movement is currently the subject of intense research. While it was believed for a long time that dynein motors are relatively weak in terms of the force they can generate, recent studies have shown that interactions with regulatory proteins confer large stall forces comparable to those of kinesin. This paper reports on a theoretical study which suggests that these large stall forces may be the result of an emergent, ATP-dependent, bistability resulting in a dynamic catch-bonding behavior that can cause the motor to switch between high and low load-force states.

Impact of noise on the regulation of intracellular transport of intermediate filaments

“…An asymmetric case is chosen for motors; the dynein stall force is assumed to be larger than the kinesin one |F sD | ¡ |F sK | as well as its forward and backward speeds (Table 1). Hence, the dynein stall to detachment force ratio is the largest; dynein is set to be the strongest motor as demonstrated in vitro [46,47].…”

“…There are several good review articles which categorize the models into continuum ratchet [10,11,12], discrete stochastic models [10,11], and models which consider conformational changes [12]. There are phenomenological models [13,14] and structural models [15,16,17]. The models that are most closely related to the work here are models which consider ensembles of motors [11,18,19,20,21,22].…”

Simulations suggest robust microtubule attachment of kinesin and dynein in antagonistic pairs

“…To test this possibility, we investigated whether either altering the load-dependent detachment kinetics of DDB or including experimentally observed pausing and diffusive states of the DDB complex could better align the simulations with the experiments. There is abundant evidence in the literature that dynein alone has catch-bond behavior, meaning that the detachment rate slows down with increasing load (19,22,(47)(48)(49)(50). To our knowledge, there is no experimental evidence that activated dynein in a DDB complex shows catch bond behavior, but there is only one published study directly addressing this question (26).…”