Regulation of microtubule-based transport by MAP4 Semenova, Irina; Ikeda, Kazuho; Resaul, Karim ...
Molecular biology of the cell,
2014-Oct-15, 2014-10-15, 20141015, Letnik:
25, Številka:
20
Journal Article
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Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here ...we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2-dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2-based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2-dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect.
Network robustness against attacks has been widely studied in fields as diverse as the Internet, power grids and human societies. But current definition of robustness is only accounting for half of ...the story: the connectivity of the nodes unaffected by the attack. Here we propose a new framework to assess network robustness, wherein the connectivity of the affected nodes is also taken into consideration, acknowledging that it plays a crucial role in properly evaluating the overall network robustness in terms of its future recovery from the attack. Specifically, we propose a dual perspective approach wherein at any instant in the network evolution under attack, two distinct networks are defined: (i) the Active Network (AN) composed of the unaffected nodes and (ii) the Idle Network (IN) composed of the affected nodes. The proposed robustness metric considers both the efficiency of destroying the AN and that of building-up the IN. We show, via analysis of well-known prototype networks and real world data, that trade-offs between the efficiency of Active and Idle Network dynamics give rise to surprising robustness crossovers and re-rankings, which can have significant implications for decision making.
Recruitment of external plus‐end directed microtubule motor kinesin‐1 to the surface of pigment granules transported to microtubule minus‐ends by cytoplasmic dynein in melanophores creates a ...tug‐of‐war between opposing microtubule motors in vivo. Loading with kinesin‐1 attenuates minus‐end directed runs of pigment granules generated by dynein, and reverses the overall direction of their movement. Therefore, in the absence of external signals, a tug‐of‐war between opposing microtubule motors is sufficient to control the directionality of microtubule transport in vivo.
Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus‐end directed kinesins and minus‐end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT‐based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug‐of‐war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug‐of‐war between opposing MT motors alone, by attaching a large number of kinesin‐1 motors to organelles transported by dynein to minus‐ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus‐end‐directed dynein‐dependent MT runs, leading to a reversal of the overall direction of dynein‐driven organelles in vivo. Therefore, in the absence of external regulators tug‐of‐war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo.
Microtubule (MT)-based organelle transport is driven by MT motor proteins that move cargoes toward MT minus-ends clustered in the cell center (dyneins) or plus-ends extended to the periphery ...(kinesins). Cells are able to rapidly switch the direction of transport in response to external cues, but the signaling events that control switching remain poorly understood. Here, we examined the signaling mechanism responsible for the rapid activation of dynein-dependent MT minus-end-directed pigment granule movement in Xenopus melanophores (pigment aggregation). We found that, along with the previously identified protein phosphatase 2A (PP2A), pigment aggregation signaling also involved casein kinase 1ε (CK1ε), that both enzymes were bound to pigment granules, and that their activities were increased during pigment aggregation. Furthermore we found that CK1ε functioned downstream of PP2A in the pigment aggregation signaling pathway. Finally, we discovered that stimulation of pigment aggregation increased phosphorylation of dynein intermediate chain (DIC) and that this increase was partially suppressed by CK1ε inhibition. We propose that signal transduction during pigment aggregation involves successive activation of PP2A and CK1ε and CK1ε-dependent phosphorylation of DIC, which stimulates dynein motor activity and increases minus-end-directed runs of pigment granules.
Actin filaments that serve as “rails” for the myosin-based transport of membrane organelles 1–4 continuously turn over by concurrent growth and shortening at the opposite ends 5. Although it is known ...that dynamics of actin filaments is essential for many of the actin cytoskeleton functions, the role of such dynamics in myosin-mediated organelle transport was never studied before. Here, we addressed the role of turnover of actin filaments in the myosin-based transport of membrane organelles by treating cells with the drugs that suppress actin-filament dynamics and found that such a suppression significantly inhibited organelle transport along the actin filaments without inhibiting their intracellular distribution or the activity of the myosin motors. We conclude that dynamics of actin filaments is essential for myosin-based transport of membrane organelles and suggest a previously unknown role of actin-filament dynamics in providing the “rails” for continuous organelle movement resulting in the increased distances traveled by membrane organelles along the actin filaments.
Earthquake clustering properties are investigated in relation to fluid balance H(t) (the difference of fluid injection and production rates) using about nine years of data from The Geysers (both the ...entire field and a local subset), Coso, and Salton Sea geothermal fields in California. Individual earthquake clusters are identified and classified using the nearest‐neighbor approach of Zaliapin and Ben‐Zion (2013a, https://doi.org/10.1785/0120150211, 2013b, https://doi.org/10.1093/gji/ggw300). These are used to calculate nine complementary cluster statistics as time series with a step of about one month. Three alternative techniques (moving window correlation, analysis of variance, and regression) are employed to assess the relations between (possibly nonstationary) time series of cluster statistics and H(t). A total of 108 pairwise relations between cluster statistics and H(t) are analyzed to clarify effects of fluid activities on seismicity in different places. The seismic clustering response to the fluid balance differs among the examined fields. The Geysers and Salton Sea areas display the highest and lowest clustering responses, respectively. The proportion of clusters consisting of a single event with no offspring (singles) is correlated significantly with H(t) at all examined data sets, with a lower proportion of singles during periods of high fluid balance. This may reflect increased susceptibility to earthquake triggering in time intervals with high injection rates. The background seismicity rates significantly increase with H(t) at the Geysers and Coso, while an opposite relation holds at the Salton Sea. This could be related to the high structural and tectonic complexity at the Salton Sea compared to the other two geothermal fields.
Key Points
Earthquake clustering responds differently to hydraulic operations at The Geysers, Coso, and Salton Sea geothermal fields
The variations of the response are likely related to different local tectonic processes and structures
Background earthquake rates and types of clusters change between periods of low and high injection‐production fluid balance
We study self-similarity in random binary rooted trees. In a well-understood case of Galton–Watson trees, a distribution on a space of trees is said to be self-similar if it is invariant with respect ...to the operation of pruning, which cuts the tree leaves. This only happens for the critical Galton–Watson tree (a constant process progeny), which also exhibits other special symmetries. We extend the prune-invariance setup to arbitrary binary trees with edge lengths. In this general case the class of self-similar processes becomes much richer and covers a variety of practically important situations. The main result is construction of the hierarchical branching processes that satisfy various self-similarity definitions (including mean self-similarity and self-similarity in edge-lengths) depending on the process parameters. Taking the limit of averaged stochastic dynamics, as the number of trajectories increases, we obtain a deterministic system of differential equations that describes the process evolution. This system is used to establish a phase transition that separates fading and explosive behavior of the average process progeny. We describe a class of critical Tokunaga processes that happen at the phase transition boundary. They enjoy multiple additional symmetries and include the celebrated critical binary Galton–Watson tree with independent exponential edge length as a special case. Finally, we discuss a duality between trees and continuous functions, and introduce a class of extreme-invariant processes, constructed as the Harris paths of a self-similar hierarchical branching process, whose local minima has the same (linearly scaled) distribution as the original process.
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