Organelle dynamics in lobster axons: anterograde, retrograde and stationary mitochondria

Forman, David S.; Lynch, Kathryn; Smith, Richard S.

doi:10.1016/0006-8993(87)91443-0

Cited by 58 publications

(50 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria are membranous organelles synthesized in the cell body and transported into axons and dendrites. Axonal transport of mitochondria have been studied in detail by Martz et al [1984] and by Forman et al [1987], both studies described that at any given moment, most of mitochondria in the axon were stationary and that moving mitochondria were seen to stop for long periods of time. These considerations are important in the light of the MAP2 and TAU effects on the binding of microtubules to mitochondria, which in principle will be consistent with the function of these molecules as anchoring structures that inhibit movement.…”

Section: Discussionmentioning

confidence: 98%

“…Microtubule-organelle binding assays have been used for identifying the proteins that participate in the formation of microtubule-organelle complexes [Sherline et al, 1977;Suprenant and Dentler, 1982;Mithieux et al, 1988;Rothwell et al, 1989;Van Der Sluijs et al, 1990;Coffe and Raymond, 1990;Severin et al, 19911. Considering the functional significance of in situ complexes observed between mitochondria and microtubules we initiated studies on the in vitro interaction of microtubules with rat brain mitochondria. In neurons, mitochondria can move from the cell body toward either the dendritic or the axonal projections, or they can be stationary in the subaxolemmal region of the plasma membrane [Forman et al, 1987;Raine et al, 19871. In previous work, we have shown that the two more abundant brain MAPs, MAP2 and TAU proteins are able to bind to rat brain mitochondria.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interaction of brain mitochondria with microtubules reconstituted from brain tubulin and MAP2 or TAU

Jung

Filliol

Miehe

et al. 1993

Cell Motil. Cytoskeleton

View full text Add to dashboard Cite

To explore the behaviour of microtubule-associated proteins, MAP2 and TAU in the interactions of mitochondria with microtubules, an homologous acellular system has been reconstituted with organelles isolated from rat brain. We have established a quantitative in vitro binding assay based on the cosedimentation of 125I-labeled microtubules with mitochondria. We found that binding of microtubules to mitochondria was concentration dependent and saturable. Binding was insensitive to ATP. A comparison of taxol-stabilized microtubules prepared from MAP-free tubulin or tubulin coated with TAU or MAP2 showed that the microtubule-associated proteins diminished, or reduced to background levels, the formation of complexes with mitochondria. In contrast, the amount of MAP-free taxol microtubules that cosedimented with mitochondria increased two- and six-fold when mitochondria were coated with MAP2 or TAU. These studies suggest that the two major brain MAPs could have a crosslinking or a spacing role, depending on their organelle localization.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Interaction of brain mitochondria with microtubules reconstituted from brain tubulin and MAP2 or TAU

Jung

Filliol

Miehe

et al. 1993

Cell Motil. Cytoskeleton

View full text Add to dashboard Cite

show abstract

“…30 which shows the internal structure of an axon. The size of common vesicles (≈ 100 nm [127]) is not negligible in front of MT interspacing. Neurofilaments also limit the available space [58].…”

Section: Confinementmentioning

confidence: 98%

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

2015

View full text Add to dashboard Cite

Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized.The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the 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. The interest for this type of question was enhanced when it was discovered that intracellular transport 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. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some 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. Some important characteristics of axonal transport is that it takes place in a confined environment; Besides several types of motors are involved, that move in opposite directions. It is a challenge to understand how this bidirectional transport is organized. We review several features that could contribute to the efficiency of bidirectional transport in the axon, including in particular the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we also discuss some open questions that may be relevant for future research in this field.

show abstract

“…We suggest that mitochondria with fresh, cell body-derived components generate a local signal that represses cytoplasmic dynein, activates kinesin-1, and thus dictates anterograde transport toward the terminal. In the axon, areas requiring ATP generate local signals that convert anterograde mitochondria to stationary by activating static cross-links with the cytoskeleton (Forman et al, 1987;Chada and Hollenbeck, 2003;Wagner et al, 2003;Miller and Sheetz, 2004;Hollenbeck and Saxton, 2005). Over time, damage to mitochondrial components from reactive oxygen species causes a decline in energy-producing capacity (Hagen et al, 1997) that triggers release from cytoskeletal anchoring, activation of dynein, and repression of kinesin-1.…”

Section: Directional Programmingmentioning

confidence: 99%

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

Pilling

Horiuchi

Lively

et al. 2006

MBoC

619

621

View full text Add to dashboard Cite

To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150 Glued suggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings ("organelle jams" or "clogs") caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration. INTRODUCTIONOrganelle transport is central to the organization, developmental fate, and functions of asymmetric cells. A bipolar neuron is an extreme case, with the somato-dendritic region and the axon containing different sets of proteins and organelles. In general, much of the machinery for synthesizing and recycling neuronal components is clustered near the nucleus. Because an axon, often with an axial ratio of many thousands, usually contains Ͼ99% of the neuronal cytoplasm, active transport of new components away from the cell body and of spent components and trophic materials back toward the cell body is critical. Disruptions of axonal transport are thought to contribute to the pathologies of Alzheimer's, amyotrophic lateral sclerosis, and other neurodegenerative diseases (reviewed by Mandelkow and Mandelkow, 2002;Hirokawa and Takemura, 2005).Long-distance organelle transport in axons is driven by motor proteins that move along parallel microtubules whose plus ends are mostly oriented toward the axon terminal (reviewed by Hollenbeck and Saxton, 2005). There are multiple types of microtubule motors in postmitotic vertebrate neurons, including kinesins that can move toward either plus-or minus-ends and at least one cytoplasmic dynein that moves toward minus-ends (Martin et al., 1999b;Hirokawa and Takemura, 2005;Hollenbeck and Saxton, 2005). Which motors bind and move which axonal components? When multiple types of motors bind a single cargo, do they collaborate or compete, how are they regulated, and how do their combined activities generate an optimal distribution of that type of cargo?Axonal mitochondria are critical for the physiology of neurons and are particularly well suited for studying active tr...

show abstract

Organelle dynamics in lobster axons: anterograde, retrograde and stationary mitochondria

Cited by 58 publications

References 40 publications

Interaction of brain mitochondria with microtubules reconstituted from brain tubulin and MAP2 or TAU

Interaction of brain mitochondria with microtubules reconstituted from brain tubulin and MAP2 or TAU

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

Contact Info

Product

Resources

About