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A budding role for a cellular dynamo
February 19, 2009Brandeis scientists identify a key cellular factor that regulates length of actin filaments
Waltham, MA-Actin, a globular protein found in all eukaryotic cells, is a workhorse that varies remarkably little from baker's yeast to the human body. Part of the cytoskeleton, actin assembles into networks of filaments that give the cell structural plasticity while driving many essential functions, from cell motility and division, to vesicle and organelle transport within the cell. In a groundbreaking new study in the current issue of Developmental Cell, Brandeis researchers raise the curtain on how this actin maintains just the right filament length to keep the cell healthy and happily dividing.
Using baker's yeast as the model organism, Brandeis researchers Melissa Chesarone, Christopher Gould, and James Moseley, all in the lab of biologist Bruce Goode, set out to discover how the length of actin fibers is controlled. By answering this question, the scientists sought to advance understanding of asymmetrical cell division, a process that not only allows yeast to divide, but also ensures the proper renewal of human stem cells and plays a crucial role in early stages of embryonic development.
In yeast cells, as in all other cells, actin fibers serve as internal "railways" or tracks that give the cell directionality and provide the wherewithal for transporting various molecular and membrane-bound cargoes from one end of the cell to the other. Molecular machines called formins produce many of the actin fibers, but in the absence of a displacement factor to put a brake on the process, formins will essentially stop at nothing, producing excessively long actin filaments at ridiculously fast rates, and wreaking cellular havoc, says Goode. In humans, genetic defects in formins are associated with conditions such as infertility and deafness.
"We wanted to know how you turn the formins off. What disrupts the interaction of the formin with the actin filament, thus terminating actin assembly and regulating its length?" Goode explained.
The researchers discovered that a protein called Bud14 is a potent inhibitor, directly binding to the formin and displacing it, thereby producing actin filaments of normal length, a prerequisite for proper actin cable architecture and cargo transport.
"In all animal, plant, and human cells, life depends on rapidly producing actin filaments of defined lengths, and we now have an important clue as to how this is regulated," said Goode. "We're now homing in on the precise mechanism by which Bud14 works and extending this analysis to mammalian cells. Once again, yeast has provided the ideal system in which to pioneer a basic problem that applies to most other species."
Brandeis University
In yeast cells, as in all other cells, actin fibers serve as internal "railways" or tracks that give the cell directionality and provide the wherewithal for transporting various molecular and membrane-bound cargoes from one end of the cell to the other. Molecular machines called formins produce many of the actin fibers, but in the absence of a displacement factor to put a brake on the process, formins will essentially stop at nothing, producing excessively long actin filaments at ridiculously fast rates, and wreaking cellular havoc, says Goode. In humans, genetic defects in formins are associated with conditions such as infertility and deafness.
"We wanted to know how you turn the formins off. What disrupts the interaction of the formin with the actin filament, thus terminating actin assembly and regulating its length?" Goode explained.
The researchers discovered that a protein called Bud14 is a potent inhibitor, directly binding to the formin and displacing it, thereby producing actin filaments of normal length, a prerequisite for proper actin cable architecture and cargo transport.
"In all animal, plant, and human cells, life depends on rapidly producing actin filaments of defined lengths, and we now have an important clue as to how this is regulated," said Goode. "We're now homing in on the precise mechanism by which Bud14 works and extending this analysis to mammalian cells. Once again, yeast has provided the ideal system in which to pioneer a basic problem that applies to most other species."
Brandeis University
Actin Filaments Current Events and Actin Filaments News RSSStudy shows how disruption of spectrin-actin network causes lens cells in the eye to lose shape
A network of proteins underlying the plasma membrane keeps epithelial cells in shape and maintains their orderly hexagonal packing in the mouse lens, say Nowak et al.
Building memories with actin
Memories aren't made of actin filaments. But their assembly is crucial for long-term potentiation (LTP), an increase in synapse sensitivity that researchers think helps to lay down memories.
Intestinal cells surprisingly active in pursuit of nutrition and defense
Every cell lining the small intestine bristles with thousands of tightly packed microvilli that project into the gut lumen, forming a brush border that absorbs nutrients and protects the body from intestinal bacteria.
Mayo Clinic researchers discover and manipulate molecular interplay that moves cancer cells
Based on research that reveals new insight into mechanisms that allow invasive tumor cells to move, researchers at the Mayo Clinic campus in Florida have a new understanding about how to stop cancer from spreading. A cancer that spreads elsewhere in the body, known as metastasis, is the process that most often leads to death from the disease.
From mother to daughters: A central mystery in cell division solved
Researchers from the Ludwig Institute for Cancer Research at the University of California, San Diego School of Medicine have identified a key step required for cell division in a study that could help improve therapies to treat cancer.
Rong Li Lab probes mechanism of asymmetry in meiotic cell division
The Stowers Institute's Rong Li Lab has characterized a mechanism that allows for asymmetrical cell division during meiosis in oocytes. By tracking chromosome movement in live mouse oocytes, the team discovered that chromosomes can recruit to their vicinity a protein called formin-2.
Understanding the migration of cancer cells
Lamellipodia are veil-shaped protrusions of the plasma membrane, that can turn into upward-curled ruffles if they fail to adhere to the substrate.
Cell surface receptors are all 'talk' in T cell stimulation
Understanding the mechanisms that drive healthy immune responses is important when it comes to combating autoimmune diseases, which occur when cells that should attack invading organisms turn on the body instead.
Penn researchers discover 'modus operandi' of heart muscle protein
Researchers at the University of Pennsylvania School of Medicine have discovered that a protein called leiomodin (Lmod) promotes the assembly of an important heart muscle protein called actin. What's more, Lmod directs the assembly of actin to form the pumping unit of the heart. The findings appear in this week's issue of Science.
Newly defined signaling pathway could mean better biofuel sources
A newly defined biochemical pathway in plants may provide the scientific tools to design plants that will yield larger quantities of alternative transportation fuels than currently can be produced, according to Purdue University researchers.
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Nanoneuroscience: Structural and Functional Roles of the Neuronal Cytoskeleton in Health and Disease (Biological and Medical Physics, Biomedical Engineering) by Nancy J. Woolf (Author), Avner Priel (Author), Jack A. Tuszynski (Author) Nanoneuroscience is the study of computationally relevant biomolecules found inside neurons. Because of recent technological advances at the nanometer scale, scientists have at their disposal increasingly better ways to study the brain and the biophysics of its molecules. This book describes how biomolecules contribute to the operations of synapses and perform other computationally relevant functions inside dendrites. These biomolecular operations considerably expand the brain-computer analogy - endowing each neuron with the processing power of a silicon-based multiprocessor. Amazingly, the brain contains hundreds of billions of neurons. | |
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Actin: Biophysics, Biochemistry and Cell Biology (Advances in Experimental Medicine and Biology) by James E. Estes (Editor), Paul J. Higgins (Editor) V.A. Medical Center, Albany, New York. Proceedings of an International Conference on the Biophysics, Biochemistry, and Cell Biology of Actin, held August 5-9, 1992, in Troy, New York. 58 contributors, 36 U.S. | |
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Mechanism of Myofilament Sliding in Muscle Contraction (Advances in Experimental Medicine and Biology) by Haruo Sugi (Editor), Gerald H. Pollack (Editor) |
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