Filament-Filament Switching Can Be Regulated by Separation Between Filaments Together with Cargo Motor Number

How intracellular transport controls the probability that cargos switch at intersections between filaments is not well understood. In one hypothesis some motors on the cargo attach to one filament while others attach to the intersecting filament, and the ensuing tug-of-war determines which filament is chosen. We investigate this hypothesis using 3D computer simulations, and discover that switching at intersections increases with the number of motors on the cargo, but is not strongly dependent on motor number when the filaments touch. Thus, simply controlling the number of active motors on the cargo cannot account for in vivo observations that found reduced switching with increasing motor number, suggesting additional mechanisms of regulation. We use simulations to show that one possible way to regulate switching is by simultaneously adjusting the separation between planes containing the crossing filaments and the total number of active motors on the cargo. Heretofore, the effect of filament-filament separation on switching has been unexplored. We find that the switching probability decreases with increasing filament separation. This effect is particularly strong for cargos with only a modest number of motors. As the filament separation increases past the maximum head-to-head distance of the motor, individual motors walking along a filament will be unable to reach the intersecting filament. Thus, any switching requires that other motors on the cargo attach to the intersecting filament and haul the cargo along it, while motor(s) engaged on the original filament detach. Further, if the filament separation is large enough, the cargo can have difficult

Biogenesis of the multifunctional lipid droplet: lipids, proteins, and sites

Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply lipids in all eukaryotic and some prokaryotic cells for energy metabolism, membrane synthesis, and production of essential lipid-derived molecules. Interest in the organelle's cell biology has exponentially increased over the last decade due to the link between LDs and prevalent human diseases and the discovery of new and unexpected functions of LDs. As a result, there has been significant recent progress toward understanding where and how LDs are formed, and the specific lipid pathways that coordinate LD biogenesis

Cargo Transport: Two Motors Are Sometimes Better Than One

Molecular motor proteins are crucial for the proper distribution of organelles and vesicles in cells. Much of our current understanding of how motors function stems from studies of single motors moving cargos in vitro. More recently, however, there has been mounting evidence that the cooperation of multiple motors in moving cargos and the regulation of motor–filament affinity could be key mechanisms that cells utilize to regulate cargo transport. Here, we review these recent advances and present a picture of how the different mechanisms of regulating the number of motors moving a cargo could facilitate cellular functions

Interpretation of High Energy String Scattering in terms of String Configurations

High energy string scattering at fixed momentum transfer, known to be dominated by Regge trajectory exchange, is interpreted by identifying families of string states which induce each type of trajectory exchange. These include the usual leading trajectory $\alpha(t)=\alpha^\prime t+1$ and its daughters as well as the ``sister'' trajectories $\alpha_m(t)=\alpha(t)/m-(m-1)/2$ and their daughters. The contribution of the sister $\alpha_m$ to high energy scattering is dominated by string excitations in the $m^{th}$ mode. Thus, at large $-t$, string scattering is dominated by wee partons, consistently with a picture of string as an infinitely composite system of ``constituents'' which carry zero energy and momentum.Comment: 14 pages, phyzzx, psfig required, Florida Preprint UFIFT-94-

Coordination of opposite-polarity microtubule motors

Many cargoes move bidirectionally, frequently reversing course between plus- and minus-end microtubule travel. For such cargoes, the extent and importance of interactions between the opposite-polarity motors is unknown. In this paper we test whether opposite-polarity motors on lipid droplets in Drosophila embryos are coordinated and avoid interfering with each other's activity, or whether they engage in a tug of war. To this end we impaired the minus-end transport machinery using dynein and dynactin mutations, and then investigated whether plus-end motion was improved or disrupted. We observe a surprisingly severe impairment of plus-end motion due to these alterations of minus-end motor activity. These observations are consistent with a coordination hypothesis, but cannot be easily explained with a tug of war model. Our measurements indicate that dynactin plays a crucial role in the coordination of plus- and minus-end–directed motors. Specifically, we propose that dynactin enables dynein to participate efficiently in bidirectional transport, increasing its ability to stay “on” during minus-end motion and keeping it “off” during plus-end motion

Flat-space scattering and bulk locality in the AdS/CFT correspondence

The large radius limit in the AdS/CFT correspondence is expected to provide a holographic derivation of flat-space scattering amplitudes. This suggests that questions of locality in the bulk should be addressed in terms of properties of the S-matrix and their translation into the conformal field theory. There are, however, subtleties in this translation related to generic growth of amplitudes near the boundary of anti de-Sitter space. Flat space amplitudes are recovered after a delicate projection of CFT correlators onto normal-mode frequencies of AdS. Once such amplitudes are obtained from the CFT, possible criteria for approximate bulk locality include bounds on growth of amplitudes at high energies and reproduction of semiclassical gravitational scattering at long distances.Comment: 25 pages, harvmac. v2: Very minor corrections to eqs. v3: Minor improvements of discussion of locality bounds and string scattering v4. Typos fixe

High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport

High-resolution particle tracking shows a specific role for the dynein regulatory factor LIS1 in high-load axonal transport of large vesicles but no evidence for mechanical activation of opposite-directed motors

Interactions and regulation of molecular motors in Xenopus melanophores

Many cellular components are transported using a combination of the actin- and microtubule-based transport systems. However, how these two systems work together to allow well-regulated transport is not clearly understood. We investigate this question in the Xenopus melanophore model system, where three motors, kinesin II, cytoplasmic dynein, and myosin V, drive aggregation or dispersion of pigment organelles called melanosomes. During dispersion, myosin V functions as a “molecular ratchet” to increase outward transport by selectively terminating dynein-driven minus end runs. We show that there is a continual tug-of-war between the actin and microtubule transport systems, but the microtubule motors kinesin II and dynein are likely coordinated. Finally, we find that the transition from dispersion to aggregation increases dynein-mediated motion, decreases myosin V–mediated motion, and does not change kinesin II–dependent motion. Down-regulation of myosin V contributes to aggregation by impairing its ability to effectively compete with movement along microtubules