scholarly journals Traffic control inside the cell: microtubule-based regulation of cargo transport

2018 ◽  
Vol 40 (2) ◽  
pp. 14-17 ◽  
Author(s):  
Linda Balabanian ◽  
Abdullah R. Chaudhary ◽  
Adam G. Hendricks
Keyword(s):  
Surface Properties ◽  
Traffic Control ◽  
Motor Proteins ◽  
Transport Proteins ◽  
Chemical Modifications ◽  
Microtubule Network ◽  
Microtubule Polymerization ◽  
Cargo Transport

The cell relies on an intricate system of molecular highways and motors to transport proteins, organelles and other vesicular cargoes to their proper locations. Microtubules, long filaments that form a network throughout the cell, act as highways. The motor proteins kinesin and dynein associate with cargoes and transport them along microtubules. Rather than simply acting as passive tracks, microtubules contain signals that regulate kinesin and dynein to target cargoes to specific locations in the cell. These signals include the organization of the microtubule network, chemical modifications that alter the microtubule surface properties and mechanics, and microtubuleassociated proteins that modulate the motility of motor proteins and microtubule polymerization.

The Kar3p and Kip2p motors function antagonistically at the spindle poles to influence cytoplasmic microtubule numbers

1998 ◽  
Vol 111 (3) ◽  
pp. 295-301 ◽  
Author(s):  
A. Huyett ◽  
J. Kahana ◽  
P. Silver ◽  
X. Zeng ◽  
W.S. Saunders
Keyword(s):  
Molecular Motors ◽  
Motor Proteins ◽  
Single Gene ◽  
Intermediate Phenotype ◽  
Microtubule Network ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cytoplasmic Microtubule ◽  
Spindle Poles ◽  
Microtubule Motors ◽  
Microtubule Growth

Microtubules provide the substrate for intracellular trafficking by association with molecular motors of the kinesin and dynein superfamilies. Motor proteins are generally thought to function as force generating units for transport of various cargoes along the microtubule polymer. Recent work suggests additional roles for motor proteins in changing the structure of the microtubule network itself. We report here that in the budding yeast Saccharomyces cerevisiae microtubule motors have antagonistic effects on microtubule numbers and lengths. As shown previously, loss of the Kar3p motor stimulates cytoplasmic microtubule growth while loss of Kip2p leads to a sharp reduction in cytoplasmic microtubule numbers. Loss of both the Kip2p and Kar3p motors together in the same cell produces an intermediate phenotype, suggesting that these two motors act in opposition to control cytoplasmic microtubule density. A Kip2p-GFP fusion from single gene expression is most concentrated at the spindle poles, as shown previously for an epitope tagged Kar3p-HA, suggesting both of these motors act from the minus ends of the microtubules to influence microtubule numbers.

scholarly journals The γTuRC Revisited: A Comparative Analysis of Interphase and Mitotic Human γTuRC Redefines the Set of Core Components and Identifies the Novel Subunit GCP8

2010 ◽  
Vol 21 (22) ◽  
pp. 3963-3972 ◽  
Author(s):  
Neus Teixidó-Travesa ◽  
Judit Villén ◽  
Cristina Lacasa ◽  
Maria Teresa Bertran ◽  
Marco Archinti ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Comparative Analysis ◽  
Protein Complex ◽  
The Novel ◽  
Microtubule Network ◽  
Microtubule Polymerization ◽  
Open Ring ◽  
Core Components ◽  
Ring Complexes ◽  
Ring Shaped Structure

The γ-tubulin complex is a multi-subunit protein complex that nucleates microtubule polymerization. γ-Tubulin complexes are present in all eukaryotes, but size and subunit composition vary. In Drosophila, Xenopus, and humans large γ-tubulin ring complexes (γTuRCs) have been described, which have a characteristic open ring-shaped structure and are composed of a similar set of subunits, named γ-tubulin, GCPs 2-6, and GCP-WD in humans. Despite the identification of these proteins, γTuRC function and regulation remain poorly understood. Here we establish a new method for the purification of native human γTuRC. Using mass spectrometry of whole protein mixtures we compared the composition of γTuRCs from nonsynchronized and mitotic human cells. Based on our analysis we can define core subunits as well as more transient interactors such as the augmin complex, which associates specifically with mitotic γTuRCs. We also identified GCP8/MOZART2 as a novel core subunit that is present in both interphase and mitotic γTuRCs. GCP8 depletion does not affect γTuRC assembly but interferes with γTuRC recruitment and microtubule nucleation at interphase centrosomes without disrupting general centrosome structure. GCP8-depleted cells do not display any obvious mitotic defects, suggesting that GCP8 specifically affects the organization of the interphase microtubule network.

scholarly journals Unravelling 3D Cargo Transport Dynamics at the Microtubule Network

2016 ◽  
Vol 110 (3) ◽  
pp. 15a
Author(s):  
Ione Verdeny Vilanova ◽  
Fabian Wehnekamp ◽  
Nitin Mohan ◽  
Ángel Sandoval Álvarez ◽  
Joe Borbely ◽  
...  
Keyword(s):  
Microtubule Network ◽  
Transport Dynamics ◽  
Cargo Transport

scholarly journals Roles of Polymerization Dynamics, Opposed Motors, and a Tensile Element in Governing the Length of Xenopus Extract Meiotic Spindles

2005 ◽  
Vol 16 (6) ◽  
pp. 3064-3076 ◽  
Author(s):  
T. J. Mitchison ◽  
P. Maddox ◽  
J. Gaetz ◽  
A. Groen ◽  
M. Shirasu ◽  
...  
Keyword(s):  
Steady State ◽  
Relative Stability ◽  
Motor Proteins ◽  
Microtubule Dynamics ◽  
Microtubule Polymerization ◽  
Hexylene Glycol ◽  
Meiotic Spindles

Metaphase spindles assemble to a steady state in length by mechanisms that involve microtubule dynamics and motor proteins, but they are incompletely understood. We found that Xenopus extract spindles recapitulate the length of egg meiosis II spindles, by using mechanisms intrinsic to the spindle. To probe these mechanisms, we perturbed microtubule polymerization dynamics and opposed motor proteins and measured effects on spindle morphology and dynamics. Microtubules were stabilized by hexylene glycol and inhibition of the catastrophe factor mitotic centromere-associated kinesin (MCAK) (a kinesin 13, previously called XKCM) and destabilized by depolymerizing drugs. The opposed motors Eg5 and dynein were inhibited separately and together. Our results are consistent with important roles for polymerization dynamics in regulating spindle length, and for opposed motors in regulating the relative stability of bipolar versus monopolar organization. The response to microtubule destabilization suggests that an unidentified tensile element acts in parallel with these conventional factors, generating spindle shortening force.

scholarly journals Theory of microtubule length regulation in antiparallel overlaps

2019 ◽  
Author(s):  
Hui-Shun Kuan ◽  
Meredith D. Betterton
Keyword(s):  
Steady State ◽  
Cell Division ◽  
Mitotic Spindle ◽  
Motor Proteins ◽  
Critical Concentration ◽  
Binding Kinetics ◽  
Kinesin Motor ◽  
Microtubule Polymerization ◽  
Length Regulation ◽  
Theory And Experiment

AbstractDuring cell division, microtubules in the mitotic spindle form antiparallel overlaps near the center of the spindle. Kinesin motor proteins alter microtubule polymerization dynamics to regulate the length of these overlaps to maintain spindle integrity. Length regulation of antiparallel overlaps has been reconstituted with purified microtubules, crosslinkers, and motors. Here we develop a theory of steady-state overlap length which depends on the filament plus-end motor concentration, determined by a balance between motor arrival (motor binding and stepping in the overlap) and motor departure (motor unbinding from filament tips during depolymerization) in the absence of motor-driven sliding. Assuming that motors processively depolymerize and exhibit altered binding kinetics near MT plus-ends improves the agreement between theory and experiment. Our theory explains the origin of the experimentally observed critical concentration, a minimum motor concentration to observe a steady-state overlap length.

Chemical modifications and surface properties of carbon blacks

Carbon ◽  
1996 ◽  
Vol 34 (12) ◽  
pp. 1521-1529 ◽  
Author(s):  
E. Papirer ◽  
R. Lacroix ◽  
J.-B. Donnet
Keyword(s):  
Surface Properties ◽  
Chemical Modifications ◽  
Carbon Blacks

scholarly journals Microtubule polymerization state and clathrin-dependent internalization regulate dynamics of cardiac potassium channel

2019 ◽  
Author(s):  
Dario Melgari ◽  
Camille Barbier ◽  
Gilles Dilanian ◽  
Catherine Rücker-Martin ◽  
Nicolas Doisne ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Functional Expression ◽  
Delayed Rectifier ◽  
Atrial Remodeling ◽  
Microtubule Network ◽  
Cardiac Electrical Activity ◽  
Delayed Rectifier Current ◽  
Microtubule Disruption ◽  
Microtubule Polymerization ◽  
Ion Channel Trafficking

ABSTRACTIon channel trafficking powerfully influences cardiac electrical activity as it regulates the number of available channels at the plasma membrane. Studies have largely focused on identifying the molecular determinants of the trafficking of the atria-specific KV1.5 channel, the molecular basis of the ultra-rapid delayed rectifier current IKur. Besides, regulated KV1.5 channel recycling upon changes in homeostatic state and mechanical constraints in native cardiomyocytes has been well documented. Here, using cutting-edge imaging in live myocytes, we investigated the dynamics of this channel in the plasma membrane. We demonstrate that the clathrin pathway is a major regulator of the functional expression of KV1.5 channels in atrial myocytes, with the microtubule network as the prominent organizer of KV1.5 transport within the membrane. Both clathrin blockade and microtubule disruption result in channel clusturization with reduced membrane mobility and internalization, whereas disassembly of the actin cytoskeleton does not. Mobile KV1.5 channels are associated with the microtubule plus-end tracking protein EB1 whereas static KV1.5 clusters are associated with stable acetylated microtubules. In human biopsies from patients in atrial fibrillation associated with atrial remodeling, drastic modifications in the trafficking balance occurs together with alteration in microtubule polymerization state resulting in modest reduced endocytosis and increased recycling. Consequently, hallmark of atrial KV1.5 dynamics within the membrane is clathrin- and microtubule-dependent. During atrial remodeling, predominance of anterograde trafficking activity over retrograde trafficking could result in accumulation ok KV1.5 channels in the plasma membrane.

scholarly journals Pericentrin is a Kinesin-1 Activator that Drives Centriole Motility

2022 ◽  
Author(s):  
Matthew R Hannaford ◽  
Rong Liu ◽  
Neil Billington ◽  
Zachary T Swider ◽  
Brian J Galletta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Motor Proteins ◽  
Motor Protein ◽  
Binding Domain ◽  
Microtubule Network ◽  
Age Dependent ◽  
Stem Cell Division ◽  
Dependent Transport

Centrosome positioning is essential for their function. Typically, centrosomes are transported to various cellular locations through the interaction of centrosome nucleated microtubules with motor proteins. However, it remains unknown how centrioles migrate in cellular contexts in which centrioles do not nucleate microtubules. Here, we demonstrate that during interphase inactive centrioles move directly along the noncentrosomal microtubule network as cargo for the motor protein Kinesin-1. We identify Pericentrin-Like-Protein (PLP) as a novel Kinesin-1 interacting molecule essential for centriole motility. PLP directly interacts with the cargo binding domain of Kinesin-1 and they comigrate on microtubules in vitro. Finally, we demonstrate that PLP-Kinesin-1 dependent transport is essential for centrosome asymmetry age dependent centrosome inheritance in asymmetric stem cell division.

scholarly journals Extreme value analysis of intracellular cargo transport by motor proteins

2021 ◽  
Author(s):  
Takuma Naoi ◽  
Yuki Kagawa ◽  
Kimiko Nagino ◽  
Shinsuke Niwa ◽  
Kumiko Hayashi
Keyword(s):  
Cell Body ◽  
Motor Proteins ◽  
Living Cells ◽  
Extreme Value ◽  
Extreme Value Analysis ◽  
Disaster Prevention ◽  
Value Analysis ◽  
Axon Terminals ◽  
Cargo Transport ◽  
Synaptic Region

In the long axon of a neuron, cargo transport between the cell body and terminal synaptic region are mainly supported by the motor proteins kinesin and dynein, which are nano-sized drivers. Synaptic materials packed as cargos are anterogradely transported to the synaptic region by kinesin, whereas materials accumulated at the axon terminals are returned to the cell body by dynein. Extreme value analysis, typically used for disaster prevention in our society, was applied to analyze the velocity of kinesin and dynein nanosized drivers to disclose their physical properties in living cells.

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