Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Molecule tracking reveals mechanism of chromosome separation in dividing cells

Molecule tracking reveals mechanism of chromosome separation in dividing cells

March 09, 2009

Reasons proposed for strong but dynamic attachment of spindle fibers

University of Washington (UW) researchers are helping to write the operating manual for the nano-scale machine that separates chromosomes before cell division. The apparatus is called a spindle because it looks like a tiny wool-spinner with thin strands of microtubules or spindle fibers sticking out. The lengthening and shortening of microtubules is thought to help push and pull apart chromosome pairs.




Understanding how this machine accurately and evenly divides genetic material is essential to learning why its parts sometimes fail. Certain cancers or birth defects, like Down syndrome or Trisomy 18, result from an uneven distribution of chromosomes.

In a study published March 6 in the journal Cell, a team led by UW scientists reports on the workings of a key component of this machine. Named a kinetochore, it is a site on each chromosome that mechanically couples to spindle fibers.

"Kineochores are also regulatory hubs," the researchers noted. "They control chromosome movements through the lengthening and shortening of the attached microtubules. They sense and correct errors in attachment. They emit a "wait" signal until the microtubules properly attach." Careful control over microtubules, they added, is vital for accurate splitting of the chromosomes.

The lead researchers on the study were Andrew F. Powers and Andrew D. Frank from the UW Department of Physiology and Biophysics and Daniel R. Gestaut, from the UW Department of Biochemistry. The senior authors of the study were Charles "Chip" Asbury, assistant professor, and Linda Wordeman, associate professor, both of physiology and biophysics and both members of the UW Center for Cell Dynamics; and Trisha Davis, professor of biochemistry, and director of the Yeast Resource Center.

Asbury is known for research on molecular machines and motors, Wordeman for work on chromosome movement, and Davis for studies of spindle poles. All are part of the Seattle Mitosis Club led by Sue Biggins at the Fred Hutchinson Cancer Research Center.

To understand how the kinetochore functions, the scientists sought to uncover the basis for its most fundamental behavior: attaching microtubules. The most puzzling aspect of this attachment, according to the researchers, is that the kinetochore has to be strong yet dynamic. It has to keep a grip on the microtubule filaments even as they add and remove their subunits.

"This ability," the researchers said, "allows the kinetochore to harness microtubule shortening and lengthening to drive the movement of chromosomes."

The same coupling behavior is found in living things from yeast cells to humans, indicating that it was conserved during evolution as a good way of getting the job done.

The question is how this mechanism works. Previous studies implicated a large, multiprotein complex, Ndc80, as a direct contact point between kinetochores and microtubules. However, researchers had only a static view of the complex. The UW researchers used special techniques to manipulate and track the activity of the complex in a laboratory set-up.

The researchers were able to show that the Ndc80 complex was indeed capable of forming dynamic, load-bearing attachments to the tips of the microtubules, probably by forming an array of individually weak microtubule binding elements that rapidly bind and unbind, but with a total energy large enough to hold on. The mechanism will produce a molecular friction that resists translocation of the microtubule through the attachment site. Other scientists have dubbed the mechanism a "slip clutch."

This kind of coupler, the researchers added, is able to remain continuously attached to the microtubule tip during both its assembly and disassembly phases. The coupler also can harness the energy released during disassembly to produce mechanical force. Coupling may depend on positively charged areas on the complex that interact with negatively charged hooks on the microtubules by electrostatic force.

Based on their findings, the scientists propose arrays of Ndc80 complexes supply the combination of plasticity and strength that allows kinetechores to hold on loosely but not let go of the tips of the microtubules.

University of Washington



Related Microtubules Current Events and Microtubules News Articles Microtubules Current Events and Microtubules News RSS Microtubules Current Events and Microtubules News RSS
Trial of new treatment for advanced melanoma shows rapid shrinking of tumors
Researchers have made significant advances in the treatment of metastatic malignant melanoma - one of the most difficult cancers to treat successfully once it has started to spread.

Newly Discovered Mechanism in Cell Division has Implications for Understanding Aberrant Chromosome's Role in Cancer, According to Penn Study
"A biologist, a physicist, and a nanotechnologist walk into a ..." sounds like the start of a joke. Instead, it was the start of a collaboration that has helped to decipher a critical, but so far largely unstudied, phase of how cells divide.

Researchers identify new function for protein missing in Duchenne muscular dystrophy
Researchers at the University of Minnesota and National Institutes of Health have identified a new function for the protein missing in people with the most common and ultimately lethal form of childhood muscular dystrophy.

EphA2-targeted therapy delivers chemo directly to ovarian cancer cells
With a novel therapeutic delivery system, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center has successfully targeted a protein that is over-expressed in ovarian cancer cells.

Advance in understanding cellulose synthesis
Cellulose is a fibrous molecule that makes up plant cell walls, gives plants shape and form and is a target of renewable, plant-based biofuels research.

The downside of microtubule stability
Stalled microtubules might be responsible for some cases of the neurological disorder Charcot-Marie-Tooth (CMT) disease.

Slicing chromosomes leads to new insights into cell division
By using ultrafast laser pulses to slice off pieces of chromosomes and observe how the chromosomes behave, biomedical engineers at the University of Michigan have gained pivotal insights into mitosis, the process of cell division.

Motor proteins may be vehicles for drug delivery
Specialized motor proteins that transport cargo within cells could be turned into nanoscale machines for drug delivery, according to bioengineers.

Mechanism of Alzheimer's suggests combination therapy needed
Researchers at the University of Illinois at Chicago College of Medicine have discovered a mode of action for mysterious but diagnostic protein snarls found in the brains of Alzheimer's patients that suggests a one-two punch of therapy may be needed to combat the neurodegenerative disease.

Structural polymorphism of 441-residue Tau at single residue resolution
Worldwide almost 30 million suffer from Alzheimer's disease, an irreversible, neurodegenerative condition that is eventually fatal.
More Microtubules Current Events and Microtubules News Articles
  Microtubules
by Pierre Dustin (Author)



The Role of Microtubules in Cell Biology, Neurobiology, and Oncology (Cancer Drug Discovery and Development)

The Role of Microtubules in Cell Biology, Neurobiology, and Oncology (Cancer Drug Discovery and Development)
by Antonio Tito Fojo (Author), Antonio Tito Fojo (Editor)

Microtubule Targets in Cancer Therapy presents the first comprehensive exploration of the dynamic potential of microtubules anti-cancer targets. Written by leading anti-cancer researchers, this groundbreaking volume collects the most current microtubule research available. Among the topics examined in this volume are compounds that interact with tubulin, mechanisms and regulation by microtubule-associated proteins and drugs, MAPs, the tubulin superfamily its isotopes, peptides and depsipeptides, and neurodegenerative diseases.



Microtubules

Microtubules
by Jeremy S. Hyams (Editor), Clive W. Lloyd (Editor)

Reflecting significant advances in microtubule research during the past decade, a prominent group of contributors present reviews dealing with three central topics—the biochemistry and assembly of tubulin dimer; associated proteins and regulation of microtubule function; and microtubule organization and function in the cell.

Nusap, a Novel Microtubule-Associated Protein (Map) Involved in Mitotic Spindle Organization (Acta Biomedica Lovaniensia, 286)

Nusap, a Novel Microtubule-Associated Protein (Map) Involved in Mitotic Spindle Organization (Acta Biomedica Lovaniensia, 286)
by Tim Raemaekers (Author)



  Microtubules, Part A, Volume 96 (Methods in Cell Biology)
by Leslie Wilson (Editor), John J. Correia (Editor)

There continues to be intense interest in the microtubule cytoskeleton, the assembly, structure and regulation of microtubules and the numerous motors and accessory proteins that control cell cycle, dynamics, organization and transport. The field continues to grow and explore new aspects of these issues driven immensely by developments in optical imaging and tracking techniques. This volume (complimented by the forthcoming companion volume by Cassimeris and Tran) brings together current research and protocols in the field of microtoublues in vitro and will serve as a valuable tool for cell biologists, biophysicists and pharmacologists who study the microtubule cyctoskeleton, as well as for researchers in the biomedical and biotechnology communities with interest in developing...

Microtubule Organization in Fission Yeast - A Systems Biology Approach

Microtubule Organization in Fission Yeast - A Systems Biology Approach
by Dietrich Foethke (Author)

In almost any eucaryotic cell microtubules are essential for a great variety of processes, including the separation of sister chromatids during cell division, the spatial organization of organelles within the cytoplasm, directed intracellular transport via motor proteins, and morphogenesis. The structure of the microtubule network and the regulation of its dynamics are therefore of utmost importance for the cell. In this work, the fission yeast Schizosaccharomyces pombe is used as a model organism to investigate how microtubule dynamics is controlled at the poles of an interphase cell. Experiments are combined with computer simulations to unravel the complicated interplay of cell shape, microtubule mechanics and regulatory proteins which enable the cell to establish and maintain its...

  Microtubules in microorganisms (Microbiology series)
by M. Dekker (Publisher)



Asymmetric Microtubule Pushing Forces in Nuclear Centering [A short communication from: Current Biology

Asymmetric Microtubule Pushing Forces in Nuclear Centering [A short communication from: Current Biology
by R.R. Daga (Author), A. Yonetani (Author), F. Chang (Author)

This digital document is a journal article from Current Biology, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.

Abstract:
Dynamic properties of microtubules contribute to the establishment of spatial order within cells. In the fission yeast Schizosaccharomyces pombe, interphase cytoplasmic microtubules are organized into antiparallel bundles that attach to the nuclear envelope and are needed to position the nucleus at the geometric center of the cell [1, 2]. Here, we show that after the nucleus is displaced by cell centrifugation, these microtubule bundles efficiently push the nucleus back to the center. Asymmetry in microtubule number,...

Microtubule: Webster's Timeline History, 1967 - 2007

Microtubule: Webster's Timeline History, 1967 - 2007
by Icon Group International (Author)

Webster's bibliographic and event-based timelines are comprehensive in scope, covering virtually all topics, geographic locations and people. They do so from a linguistic point of view, and in the case of this book, the focus is on "Microtubule," including when used in literature (e.g. all authors that might have Microtubule in their name). As such, this book represents the largest compilation of timeline events associated with Microtubule when it is used in proper noun form. Webster's timelines cover bibliographic citations, patented inventions, as well as non-conventional and alternative meanings which capture ambiguities in usage. These furthermore cover all parts of speech (possessive, institutional usage, geographic usage) and contexts, including pop culture, the arts, social...

Microtubule Proteins

Microtubule Proteins
by Jesus Avila (Author)

This work focuses on the structural and functional description of the microtubule proteins. The objective of the authors is to establish a relationship between the structure of microtubule proteins and the functions in which these polymers are involved. This book covers topics which have been treated only in a preliminary manner in previous works, such as microtubule dynamics and microtubule poisons. Microtubules display a variety of cellular roles and are vital for the separation and correct distribution of chromosomes during cell division. They also play an important role in morphogenesis, intracellular transport, secretion, and motility. Microtubule Proteins is a concise, easy-to-read text which is particularly of interest to cell biologists, chemists, neurochemists, and graduate...

© 2009 BrightSurf.com