3,187 research outputs found
Intracellular transport driven by cytoskeletal motors: General mechanisms and defects
Cells are strongly out-of-equilibrium systems driven by continuous energy
supply. They carry out many vital functions requiring active transport of
various ingredients and organelles, some being small, others being large. The
cytoskeleton, composed of three types of filaments, determines the shape of the
cell and plays a role in cell motion. It also serves as a road network for the
so-called cytoskeletal motors. These molecules can attach to a cytoskeletal
filament, perform directed motion, possibly carrying along some cargo, and then
detach. It is a central issue to understand how intracellular transport driven
by molecular motors is regulated, in particular because its breakdown is one of
the signatures of some neuronal diseases like the Alzheimer.
We give a survey of the current knowledge on microtubule based intracellular
transport. We first review some biological facts obtained from experiments, and
present some modeling attempts based on cellular automata. We start with
background knowledge on the original and variants of the TASEP (Totally
Asymmetric Simple Exclusion Process), before turning to more application
oriented models. After addressing microtubule based transport in general, with
a focus on in vitro experiments, and on cooperative effects in the
transportation of large cargos by multiple motors, we concentrate on axonal
transport, because of its relevance for neuronal diseases. It is a challenge to
understand how this transport is organized, given that it takes place in a
confined environment and that several types of motors moving in opposite
directions are involved. We review several features that could contribute to
the efficiency of this transport, including the role of motor-motor
interactions and of the dynamics of the underlying microtubule network.
Finally, we discuss some still open questions.Comment: 74 pages, 43 figure
A model for bidirectional traffic of cytoskeletal motors
We introduce a stochastic lattice gas model including two particle species
and two parallel lanes. One lane with exclusion interaction and directed motion
and the other lane without exclusion and unbiased diffusion, mimicking a
micotubule filament and the surrounding solution. For a high binding affinity
to the filament, jam-like situations dominate the system's behaviour. The
fundamental process of position exchange of two particles is approximated. In
the case of a many-particle system, we were able to identify a regime in which
the system is rather homogenous presenting only small accumulations of
particles and a regime in which an important fraction of all particles
accumulates in the same cluster. Numerical data proposes that this cluster
formation will occur at all densities for large system sizes. Coupling of
several filaments leads to an enhanced cluster formation compared to the
uncoupled system, suggesting that efficient bidirectional transport on
one-dimensional filaments relies on long-ranged interactions and track
formation.Comment: 20 pages, 9 figure
Particle interactions and lattice dynamics: Scenarios for efficient bidirectional stochastic transport?
Intracellular transport processes driven by molecular motors can be described
by stochastic lattice models of self-driven particles. Here we focus on
bidirectional transport models excluding the exchange of particles on the same
track. We explore the possibility to have efficient transport in these systems.
One possibility would be to have appropriate interactions between the various
motors' species, so as to form lanes. However, we show that the lane formation
mechanism based on modified attachment/detachment rates as it was proposed
previously is not necessarily connected to an efficient transport state and is
suppressed when the diffusivity of unbound particles is finite. We propose
another interaction mechanism based on obstacle avoidance that allows to have
lane formation for limited diffusion. Besides, we had shown in a separate paper
that the dynamics of the lattice itself could be a key ingredient for the
efficiency of bidirectional transport. Here we show that lattice dynamics and
interactions can both contribute in a cooperative way to the efficiency of
transport. In particular, lattice dynamics can decrease the interaction
threshold beyond which lanes form. Lattice dynamics may also enhance the
transport capacity of the system even when lane formation is suppressed.Comment: 25 pages, 17 figures, 2 table
The role of microtubule movement in bidirectional organelle transport
We study the role of microtubule movement in bidirectional organelle
transport in Drosophila S2 cells and show that EGFP-tagged peroxisomes in cells
serve as sensitive probes of motor induced, noisy cytoskeletal motions.
Multiple peroxisomes move in unison over large time windows and show
correlations with microtubule tip positions, indicating rapid microtubule
fluctuations in the longitudinal direction. We report the first high-resolution
measurement of longitudinal microtubule fluctuations performed by tracing such
pairs of co-moving peroxisomes. The resulting picture shows that
motor-dependent longitudinal microtubule oscillations contribute significantly
to cargo movement along microtubules. Thus, contrary to the conventional view,
organelle transport cannot be described solely in terms of cargo movement along
stationary microtubule tracks, but instead includes a strong contribution from
the movement of the tracks.Comment: 24 pages, 5 figure
The role of motor proteins in endosomal sorting
Abstract Microtubule motor proteins play key roles in the spatial organization of intracellular organelles as well as the transfer of material between them. This is well illustrated both by the vectorial transfer of biosynthetic cargo from the endoplasmic reticulum to the Golgi apparatus as well as the sorting of secretory and endocytic cargo in the endosomal system. Roles have been described for dynein and kinesin motors in each of these steps. Cytoplasmic dynein is a highly complex motor comprising multiple subunits that provide functional specialization. The family of human kinesins includes over 40 members. This complexity provides immense functional diversity, yet little is known of the specific requirements and functions of individual motors during discrete membrane trafficking steps. In the present paper, we describe some of the latest findings in this area that seek to define the mechanisms of recruitment and control of activity of microtubule motors in spatial organization and cargo trafficking through the endosomal network
A novel physiological role for ARF1 in the formation of bidirectional tubules from the Golgi.
Capitalizing on CRISPR/Cas9 gene-editing techniques and super-resolution nanoscopy, we explore the role of the small GTPase ARF1 in mediating transport steps at the Golgi. Besides its well-established role in generating COPI vesicles, we find that ARF1 is also involved in the formation of long (∼3 µm), thin (∼110 nm diameter) tubular carriers. The anterograde and retrograde tubular carriers are both largely free of the classical Golgi coat proteins coatomer (COPI) and clathrin. Instead, they contain ARF1 along their entire length at a density estimated to be in the range of close packing. Experiments using a mutant form of ARF1 affecting GTP hydrolysis suggest that ARF1[GTP] is functionally required for the tubules to form. Dynamic confocal and stimulated emission depletion imaging shows that ARF1-rich tubular compartments fall into two distinct classes containing 1) anterograde cargoes and clathrin clusters or 2) retrograde cargoes and coatomer clusters
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