scholarly journals Discrete regions of the kinesin-8 Kip3 tail differentially mediate astral microtubule stability and spindle disassembly

2018 ◽  
Vol 29 (15) ◽  
pp. 1866-1877 ◽  
Author(s):  
Sandeep Dave ◽  
Samuel J. Anderson ◽  
Pallavi Sinha Roy ◽  
Emmanuel T. Nsamba ◽  
Angela R. Bunning ◽  
...  
Keyword(s):  
Dynamic Properties ◽  
Microtubule Dynamics ◽  
Motor Domain ◽  
Spindle Positioning ◽  
Cellular Processes ◽  
Microtubule Stability ◽  
Astral Microtubule ◽  
Cellular Context ◽  
Spindle Disassembly ◽  
The Stability

To function in diverse cellular processes, the dynamic properties of microtubules must be tightly regulated. Cellular microtubules are influenced by a multitude of regulatory proteins, but how their activities are spatiotemporally coordinated within the cell, or on specific microtubules, remains mostly obscure. The conserved kinesin-8 motor proteins are important microtubule regulators, and family members from diverse species combine directed motility with the ability to modify microtubule dynamics. Yet how kinesin-8 activities are appropriately deployed in the cellular context is largely unknown. Here we reveal the importance of the nonmotor tail in differentially controlling the physiological functions of the budding yeast kinesin-8, Kip3. We demonstrate that the tailless Kip3 motor domain adequately governs microtubule dynamics at the bud tip to allow spindle positioning in early mitosis. Notably, discrete regions of the tail mediate specific functions of Kip3 on astral and spindle microtubules. The region proximal to the motor domain operates to spatially regulate astral microtubule stability, while the distal tail serves a previously unrecognized role to control the timing of mitotic spindle disassembly. These findings provide insights into how nonmotor tail domains differentially control kinesin functions in cells and the mechanisms that spatiotemporally control the stability of cellular microtubules.

scholarly journals Cdk1-dependent destabilization of long astral microtubules is required for spindle orientation

2020 ◽  
Author(s):  
Divya Singh ◽  
Nadine Schmidt ◽  
Franziska Müller ◽  
Tanja Bange ◽  
Alexander W. Bird
Keyword(s):  
Mitotic Spindle ◽  
Cell Shape ◽  
Microtubule Dynamics ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Spindle Positioning ◽  
Tissue Organization ◽  
Microtubule Stability ◽  
Astral Microtubule ◽  
Early Mitosis

AbstractThe precise execution of mitotic spindle orientation in response to cell shape cues is important for tissue organization and development. The presence of astral microtubules extending from the centrosome towards the cell cortex is essential for this process, but little is understood about the contribution of astral microtubule dynamics to spindle positioning, or how astral microtubule dynamics are regulated spatiotemporally. The mitotic regulator Cdk1-CyclinB promotes destabilization of centrosomal microtubules and increased microtubule dynamics as cells transition from interphase to mitosis, but how Cdk1 activity specifically modulates astral microtubule stability, and whether it impacts spindle positioning, is unknown. Here we uncover a mechanism revealing that Cdk1 destabilizes astral microtubules to ensure spindle reorientation in response to cell shape. Phosphorylation of the EB1-dependent microtubule plus-end tracking protein GTSE1 by Cdk1 in early mitosis abolishes its interaction with EB1 and recruitment to microtubule plus-ends. Loss of Cdk1 activity, or mutation of phosphorylation sites in GTSE1, induces recruitment of GTSE1 to growing microtubule plus-ends in mitosis. This decreases the catastrophe frequency of astral microtubules, and causes an increase in the number of long astral microtubules reaching the cell cortex, which restrains the ability of cells to reorient spindles along the long cellular axis in early mitosis. Astral microtubules must thus not only be present, but also dynamic to allow the spindle to reorient in response to cell shape, a state achieved by selective destabilization of long astral microtubules via Cdk1.

scholarly journals Septins: New Microtubule Interacting Partners

2008 ◽  
Vol 8 ◽  
pp. 611-620 ◽  
Author(s):  
Rosalind Silverman-Gavrila ◽  
Lorelei Silverman-Gavrila
Keyword(s):  
Neurodegenerative Diseases ◽  
Cell Shape ◽  
Therapeutic Strategies ◽  
Microtubule Dynamics ◽  
Microtubule Cytoskeleton ◽  
Microtubule Associated Proteins ◽  
Cellular Processes ◽  
Microtubule Stability ◽  
Associated Proteins ◽  
Dependent Processes

Originally characterized as regulators of cytokinesis, septins were later implicated in other cellular processes. Recent studies show that septins have a broader role in microtubule-dependent processes, such as karyokinesis, exocytosis, and maintenance of cell shape. Many members of the septin family have been shown to colocalize or interact with the microtubule cytoskeleton, suggesting that these might be general properties of septins. Septins could play an important role in regulating microtubule dynamics by interacting with microtubule-associated proteins (MAPs) that modulate microtubule stability. Being able to associate with both microtubules and actin, septins can play an important role as adaptors between the two cytoskeletons and as regulators of processes in which both actin and microtubules are involved. As septins are associated with various neurodegenerative diseases and cancer, a better understanding of the biology of septins and their interactions with microtubules is important in order to develop possible therapeutic strategies for these diseases.

scholarly journals Microtubule dynamics in fish melanophores.

1994 ◽  
Vol 126 (6) ◽  
pp. 1455-1464 ◽  
Author(s):  
V I Rodionov ◽  
S S Lim ◽  
V I Gelfand ◽  
G G Borisy
Keyword(s):  
Intracellular Transport ◽  
Time Course ◽  
Dynamic Properties ◽  
Time Lapse ◽  
Microtubule Dynamics ◽  
Charge Coupled Device ◽  
Alpha Tubulin ◽  
Acetylated Tubulin ◽  
Microtubule Stability ◽  
Pigment Distribution

We have studied the dynamics of microtubules in black tetra (Gymnocorymbus ternetzi) melanophores to test the possible correlation of microtubule stability and intracellular particle transport. X-rhodamine-or caged fluorescein-conjugated tubulin were microinjected and visualized by fluorescence digital imaging using a cooled charge coupled device and videomicroscopy. Microtubule dynamics were evaluated by determining the time course of tubulin incorporation after pulse injection, by time lapse observation, and by quantitation of fluorescence redistribution after photobleaching and photoactivation. The time course experiments showed that the kinetics of incorporation of labeled tubulin into microtubules were similar for cells with aggregated or dispersed pigment with most microtubules becoming fully labeled within 15-20 min after injection. Quantitation by fluorescence redistribution after photobleaching and photoactivation confirmed that microtubule turnover was rapid in both states, t1/2 = 3.5 +/- 1.5 and 6.1 +/- 3.0 min for cells with aggregated and dispersed pigment, respectively. In addition, immunostaining with antibodies specific to posttranslationally modified alpha-tubulin, which is usually enriched in stable microtubules, showed that microtubules composed exclusively of detyrosinated tubulin were absent and microtubules containing acetylated tubulin were sparse. We conclude that the microtubules of melanophores are very dynamic, that their dynamic properties do not depend critically on the state of pigment distribution, and that their stabilization is not a prerequisite for intracellular transport.

scholarly journals mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer

2020 ◽  
Vol 21 (18) ◽  
pp. 6648
Author(s):  
Dobrochna Dolicka ◽  
Cyril Sobolewski ◽  
Marta Correia de Sousa ◽  
Monika Gjorgjieva ◽  
Michelangelo Foti
Keyword(s):  
Liver Diseases ◽  
Binding Proteins ◽  
Current Knowledge ◽  
Cellular Processes ◽  
Complex Processes ◽  
Cellular Context ◽  
Inflammatory Processes ◽  
The Stability ◽  
And Function ◽  
Post Transcriptional Regulation

AU-rich element-binding proteins (AUBPs) represent important post-transcriptional regulators of gene expression. AUBPs can bind to the AU-rich elements present in the 3’-UTR of more than 8% of all mRNAs and are thereby able to control the stability and/or translation of numerous target mRNAs. The regulation of the stability and the translation of mRNA transcripts by AUBPs are highly complex processes that occur through multiple mechanisms depending on the cell type and the cellular context. While AUBPs have been shown to be involved in inflammatory processes and the development of various cancers, their important role and function in the development of chronic metabolic and inflammatory fatty liver diseases (FLDs), as well as in the progression of these disorders toward cancers such as hepatocellular carcinoma (HCC), has recently started to emerge. Alterations of either the expression or activity of AUBPs are indeed significantly associated with FLDs and HCC, and accumulating evidence indicates that several AUBPs are deeply involved in a significant number of cellular processes governing hepatic metabolic disorders, inflammation, fibrosis, and carcinogenesis. Herein, we discuss our current knowledge of the roles and functions of AUBPs in liver diseases and cancer. The relevance of AUBPs as potential biomarkers for different stages of FLD and HCC, or as therapeutic targets for these diseases, are also highlighted.

scholarly journals γ-Tubulin Is Required for Proper Recruitment and Assembly of Kar9–Bim1 Complexes in Budding Yeast

2006 ◽  
Vol 17 (10) ◽  
pp. 4420-4434 ◽  
Author(s):  
Lara Cuschieri ◽  
Rita Miller ◽  
Jackie Vogel
Keyword(s):  
Budding Yeast ◽  
Spindle Pole ◽  
Microtubule Dynamics ◽  
Interacting Proteins ◽  
Cortical Actin ◽  
Dynamic Interactions ◽  
Spindle Positioning ◽  
Astral Microtubule ◽  
Spindle Pole Bodies

Microtubule plus-end–interacting proteins (+TIPs) promote the dynamic interactions between the plus ends (+ends) of astral microtubules and cortical actin that are required for preanaphase spindle positioning. Paradoxically, +TIPs such as the EB1 orthologue Bim1 and Kar9 also associate with spindle pole bodies (SPBs), the centrosome equivalent in budding yeast. Here, we show that deletion of four C-terminal residues of the budding yeast γ-tubulin Tub4 (tub4-Δdsyl) perturbs Bim1 and Kar9 localization to SPBs and Kar9-dependant spindle positioning. Surprisingly, we find Kar9 localizes to microtubule +ends in tub4-Δdsyl cells, but these microtubules fail to position the spindle when targeted to the bud. Using cofluorescence and coaffinity purification, we show Kar9 complexes in tub4-Δdsyl cells contain reduced levels of Bim1. Astral microtubule dynamics is suppressed in tub4-Δdsyl cells, but it are restored by deletion of Kar9. Moreover, Myo2- and F-actin–dependent dwelling of Kar9 in the bud is observed in tub4-Δdsyl cells, suggesting defective Kar9 complexes tether microtubule +ends to the cortex. Overproduction of Bim1, but not Kar9, restores Kar9-dependent spindle positioning in the tub4-Δdsyl mutant, reduces cortical dwelling, and promotes Bim1–Kar9 interactions. We propose that SPBs, via the tail of Tub4, promote the assembly of functional +TIP complexes before their deployment to microtubule +ends.

A simulation apparatus for the experimental study of batch reactor control methods

1986 ◽  
Vol 51 (6) ◽  
pp. 1259-1267
Author(s):  
Josef Horák ◽  
Petr Beránek
Keyword(s):  
Experimental Study ◽  
Closed Loop ◽  
Dynamic Properties ◽  
Batch Reactor ◽  
Exothermic Reaction ◽  
Electric Heating ◽  
Batch Reactors ◽  
Exchange Area ◽  
The Stability ◽  
Methods Of Control

A simulation apparatus for the experimental study of the methods of control of batch reactors is devised. In this apparatus, the production of heat by an exothermic reaction is replaced by electric heating controlled by a computer in a closed loop; the reactor is cooled with an external cooler whose dynamic properties can be varied while keeping the heat exchange area constant. The effect of the cooler geometry on its dynamic properties is investigated and the effect of the cooler inertia on the stability and safety of the on-off temperature control in the unstable pseudostationary state is examined.

Modal Analyses of Deployable Truss Structures Based on Shape Memory Polymer Composites

2016 ◽  
Vol 08 (07) ◽  
pp. 1640009 ◽  
Author(s):  
Fengfeng Li ◽  
Liwu Liu ◽  
Xin Lan ◽  
Tong Wang ◽  
Xiangyu Li ◽  
...  
Keyword(s):  
Finite Element ◽  
Shape Memory ◽  
Polymer Composites ◽  
Dynamic Properties ◽  
Low Cost ◽  
Shape Memory Polymer ◽  
Truss Structures ◽  
Modal Test ◽  
The Stability ◽  
Mechanical Devices

With large spatial deployable antennas used more widely, the stability of deployable antennas is attracting more attention. The form of the support structure is an important factor of the antenna’s natural frequency, which is essential to study to prevent the resonance. The deployable truss structures based on shape memory polymer composites (SMPCs) have made themselves feasible for their unique properties such as highly reliable, low-cost, light weight, and self-deployment without complex mechanical devices compared with conventional deployable masts. This study offers deliverables as follows: an establishment of three-longeron beam and three-longeron truss finite element models by using ABAQUS; calculation of natural frequencies and vibration modes; parameter studies for influence on their dynamic properties; manufacture of a three-longeron truss based on SMPC, and modal test of the three-longeron truss. The results show that modal test and finite element simulation fit well.

scholarly journals Cellular ATP Levels Determine the Stability of a Nucleotide Kinase

2021 ◽  
Vol 8 ◽  
Author(s):  
Oliver Brylski ◽  
Puja Shrestha ◽  
Patricia Gnutt ◽  
David Gnutt ◽  
Jonathan Wolf Mueller ◽  
...  
Keyword(s):  
Protein Stability ◽  
Bound States ◽  
Atp Depletion ◽  
Aps Kinase ◽  
Cellular Processes ◽  
Atp Levels ◽  
Stability Change ◽  
Cell Stability ◽  
The Stability ◽  
Nucleotide Kinase

The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.

Nucleosome mobilization and positioning by ISWI-containing chromatin-remodeling factors

2001 ◽  
Vol 114 (14) ◽  
pp. 2561-2568
Author(s):  
Gernot Längst ◽  
Peter B. Becker
Keyword(s):  
Transcriptional Regulation ◽  
Chromatin Remodeling ◽  
Chromosome Structure ◽  
Dynamic Properties ◽  
Chromatin Assembly ◽  
Functional Characteristics ◽  
Cellular Processes

ATP-dependent chromatin-remodeling machines of the SWI/SNF family are involved in many cellular processes in eukaryotic nuclei, such as transcription, replication, repair and recombination. Remodeling factors driven by the ATPase ISWI make up a subgroup of this family that exhibits defined mechanistic and functional characteristics. ISWI-induced nucleosome mobility endows nucleosomal arrays with dynamic properties and recent results suggest that ISWI-type remodelers have diverse functions that range from transcriptional regulation to chromatin assembly and maintenance of chromosome structure.

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