Cargo Transport by Cytoplasmic Dynein Can Center Embryonic Centrosomes

Longoria, Rafael A.; Shubeita, George T.

doi:10.1371/journal.pone.0067710

Cited by 16 publications

(15 citation statements)

References 44 publications

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“…They suggested that such forces are generated by drag on trains of organelles as they are carried by microtubule motors toward minus ends that are attached to the centrosome. It has since been shown that drag on dynein-cargo complexes indeed generates important length-dependent pulling forces on microtubules whose minus ends are attached to pronuclei (35)(36)(37). Our work has focused on what is in essence the reverse process: predominantly plus-end-directed transport driven by kinesin-1 along microtubules that are attached by their minus ends to the oocyte cortex.…”

Section: Discussionmentioning

confidence: 99%

A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows

Monteith

Brunner

Djagaeva

et al. 2016

Biophysical Journal

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The transport of cytoplasmic components can be profoundly affected by hydrodynamics. Cytoplasmic streaming in Drosophila oocytes offers a striking example. Forces on fluid from kinesin-1 are initially directed by a disordered meshwork of microtubules, generating minor slow cytoplasmic flows. Subsequently, to mix incoming nurse cell cytoplasm with ooplasm, a subcortical layer of microtubules forms parallel arrays that support long-range, fast flows. To analyze the streaming mechanism, we combined observations of microtubule and organelle motions with detailed mathematical modeling. In the fast state, microtubules tethered to the cortex form a thin subcortical layer and undergo correlated sinusoidal bending. Organelles moving in flows along the arrays show velocities that are slow near the cortex and fast on the inward side of the subcortical microtubule layer. Starting with fundamental physical principles suggested by qualitative hypotheses, and with published values for microtubule stiffness, kinesin velocity, and cytoplasmic viscosity, we developed a quantitative coupled hydrodynamic model for streaming. The fully detailed mathematical model and its simulations identify key variables that can shift the system between disordered (slow) and ordered (fast) states. Measurements of array curvature, wave period, and the effects of diminished kinesin velocity on flow rates, as well as prior observations on f-actin perturbation, support the model. This establishes a concrete mechanistic framework for the ooplasmic streaming process. The self-organizing fast phase is a result of viscous drag on kinesin-driven cargoes that mediates equal and opposite forces on cytoplasmic fluid and on microtubules whose minus ends are tethered to the cortex. Fluid moves toward plus ends and microtubules are forced backward toward their minus ends, resulting in buckling. Under certain conditions, the buckling microtubules self-organize into parallel bending arrays, guiding varying directions for fast plus-end directed fluid flows that facilitate mixing in a low Reynolds number regime.

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Section: Discussionmentioning

confidence: 99%

A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows

Monteith

Brunner

Djagaeva

et al. 2016

Biophysical Journal

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“…In larger cells, such as eggs and early blastomeres of marine invertebrates, amphibians and fish, mounting evidence suggests that MT pushing is not very efficient in promoting aster centration Tanimoto et al, 2016;Wühr et al, 2010). Length-scaling in these cells is thought to be driven from dynein motors that directly pull on MTs from sites in the cytoplasm (Barbosa et al, 2017;Kimura and Kimura, 2011;Longoria and Shubeita, 2013). The mechanical coupling of dyneins to the cytoplasm is thought to be mediated by the friction of cargos or endo-membranes that are moved by dyneins to the aster center.…”

Section: Microtubule Forces As Geometrical Rulers To Target the Cell mentioning

confidence: 99%

How cells sense their own shape – mechanisms to probe cell geometry and their implications in cellular organization and function

Haupt

Minc

2018

Journal of Cell Science

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Cells come in a variety of shapes that most often underlie their functions. Regulation of cell morphogenesis implies that there are mechanisms for shape sensing that still remain poorly appreciated. Global and local cell geometry features, such as aspect ratio, size or membrane curvature, may be probed by intracellular modules, such as the cytoskeleton, reaction-diffusion systems or molecular complexes. In multicellular tissues, cell shape emerges as an important means to transduce tissue-inherent chemical and mechanical cues into intracellular organization. One emergent paradigm is that cell-shape sensing is most often based upon mechanisms of self-organization, rather than determinism. Here, we review relevant work that has elucidated some of the core principles of how cellular geometry may be conveyed into spatial information to guide processes, such as polarity, signaling, morphogenesis and division-plane positioning.

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“…The force required for MTOC convergence to the nuclear region is thought to originate from a combination of MTs, motors and anchorage points. Multiple mechanisms have been reported in the past to drive radial MT array transport in cells- (a) polymerization dependent pushing forces as seen during the centering of asters in vitro [ 11 , 12 ], (b) cortical force-generator based pulling [ 13 ], (c) cortical motors which both depolymerize and pull [ 14 ], (d) cytoplasmic minus-ended motors which pull asters in a length-dependent manner [ 15 ], (e) cytoplasmic streaming by cargo transport driving aster movement [ 16 , 17 ] and (f) acto-myosin contractility as seen in starfish oocytes [ 18 ]. Contact with the cell cortex can move asters when the relative MT lengths is comparable to the cell radius [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…However most of the cortical pushing and pulling models are unlikely to affect long-range movement of MTOCs which have MT lengths ∼3 μm as compared to the cell-radius of ∼40 μm . Transport of asters by cytoplasmic streaming based on cargo transport by one large aster [ 17 ], is also unlikely to drive mouse meiosis I oocyte MTOCs due to their size and number (∼80 to 100), which will prevent a coherent and directed flow. Inhibition of acto-myosin contractility has also been shown to have no effect on the centripetal movement of mouse MTOCs [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

A Motor-Gradient and Clustering Model of the Centripetal Motility of MTOCs in Meiosis I of Mouse Oocytes

Khetan¹,

Athale²

2016

PLoS Comput Biol

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Asters nucleated by Microtubule (MT) organizing centers (MTOCs) converge on chromosomes during spindle assembly in mouse oocytes undergoing meiosis I. Time-lapse imaging suggests that this centripetal motion is driven by a biased ‘search-and-capture’ mechanism. Here, we develop a model of a random walk in a drift field to test the nature of the bias and the spatio-temporal dynamics of the search process. The model is used to optimize the spatial field of drift in simulations, by comparison to experimental motility statistics. In a second step, this optimized gradient is used to determine the location of immobilized dynein motors and MT polymerization parameters, since these are hypothesized to generate the gradient of forces needed to move MTOCs. We compare these scenarios to self-organized mechanisms by which asters have been hypothesized to find the cell-center- MT pushing at the cell-boundary and clustering motor complexes. By minimizing the error between simulation outputs and experiments, we find a model of “pulling” by a gradient of dynein motors alone can drive the centripetal motility. Interestingly, models of passive MT based “pushing” at the cortex, clustering by cross-linking motors and MT-dynamic instability gradients alone, by themselves do not result in the observed motility. The model predicts the sensitivity of the results to motor density and stall force, but not MTs per aster. A hybrid model combining a chromatin-centered immobilized dynein gradient, diffusible minus-end directed clustering motors and pushing at the cell cortex, is required to comprehensively explain the available data. The model makes experimentally testable predictions of a spatial bias and self-organized mechanisms by which MT asters can find the center of a large cell.

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Cargo Transport by Cytoplasmic Dynein Can Center Embryonic Centrosomes

Cited by 16 publications

References 44 publications

A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows

A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows

How cells sense their own shape – mechanisms to probe cell geometry and their implications in cellular organization and function

A Motor-Gradient and Clustering Model of the Centripetal Motility of MTOCs in Meiosis I of Mouse Oocytes

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