 |
|
Penn researchers discover 'modus operandi' of heart muscle protein
April 11, 2008Implications for cardiac development and health
PHILADELPHIA - 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.
"Very little was known about Lmod when we began this study," says lead author Roberto Dominguez, PhD, Associate Professor of Physiology.
"It appeared that this protein was present in muscle cells but this had not been demonstrated directly and nobody knew what it did," explains Dominguez. "We compared the amino acid sequence of Lmod with the sequence of another protein called tropomodulin [Tmod] that was already known to bind actin filaments in muscle cells. We found that one part of Lmod was very similar to Tmod, but Lmod was a bigger protein than Tmod and contained unique features that made us suspect that it could assemble the actin filaments of the heart muscle. This is exactly what we found."
The results answer a question that scientists studying the heart have long asked: What controls the assembly of the pumping unit of the heart?
Actin is the most abundant protein in most animal cells and forms long polymers, or filaments, that make up the cell skeleton. In the cells that make up muscles and the heart, interactions of actin filaments with motor proteins produce the contractions that pump blood through the body.
Actin spontaneously forms polymers in test tubes, but living cells use nucleator proteins to control the time and place where actin filaments forms. "For a long time, physiologists have wondered what serves as the nucleator protein in cardiac muscle cells," says co-author Professor Thomas Pollard, PhD, of Yale University. "It was very satisfying after all these years to discover that Lmod can serve as the nucleator protein to initiate the forming of actin polymers in heart muscle cells."
Lmod also directs actin filaments to the sarcomere, the part of the heart that controls contractions or pumping. When Lmod was knocked down in cardiac muscle cells by an RNA silencing technique, the sarcomeres became completely disorganized and could not direct muscles to contract.
Proper localization of Lmod in heart cells is critical, because even moderately elevated levels promote the formation of abnormal actin bundles in the nuclei of cardiac muscle cells where actin does not belong. A similar disorganization of actin bundles is characteristic of a disease of skeletal muscle weakness called intranuclear rod myopathy. Although this disease is caused by a mutation in a skeletal muscle-specific actin gene, the similarity in appearance suggests that mutations in Lmod could cause the same type of disease in cardiac muscle cells.
The Penn team is currently studying how the heart regulates the level of Lmod and how Lmod might be relevant to cardiac muscle disease. In addition, the team is attempting to crystallize Lmod in order to study its structure directly.
University of Pennsylvania School of Medicine
"It appeared that this protein was present in muscle cells but this had not been demonstrated directly and nobody knew what it did," explains Dominguez. "We compared the amino acid sequence of Lmod with the sequence of another protein called tropomodulin [Tmod] that was already known to bind actin filaments in muscle cells. We found that one part of Lmod was very similar to Tmod, but Lmod was a bigger protein than Tmod and contained unique features that made us suspect that it could assemble the actin filaments of the heart muscle. This is exactly what we found."
The results answer a question that scientists studying the heart have long asked: What controls the assembly of the pumping unit of the heart?
Actin is the most abundant protein in most animal cells and forms long polymers, or filaments, that make up the cell skeleton. In the cells that make up muscles and the heart, interactions of actin filaments with motor proteins produce the contractions that pump blood through the body.
Actin spontaneously forms polymers in test tubes, but living cells use nucleator proteins to control the time and place where actin filaments forms. "For a long time, physiologists have wondered what serves as the nucleator protein in cardiac muscle cells," says co-author Professor Thomas Pollard, PhD, of Yale University. "It was very satisfying after all these years to discover that Lmod can serve as the nucleator protein to initiate the forming of actin polymers in heart muscle cells."
Lmod also directs actin filaments to the sarcomere, the part of the heart that controls contractions or pumping. When Lmod was knocked down in cardiac muscle cells by an RNA silencing technique, the sarcomeres became completely disorganized and could not direct muscles to contract.
Proper localization of Lmod in heart cells is critical, because even moderately elevated levels promote the formation of abnormal actin bundles in the nuclei of cardiac muscle cells where actin does not belong. A similar disorganization of actin bundles is characteristic of a disease of skeletal muscle weakness called intranuclear rod myopathy. Although this disease is caused by a mutation in a skeletal muscle-specific actin gene, the similarity in appearance suggests that mutations in Lmod could cause the same type of disease in cardiac muscle cells.
The Penn team is currently studying how the heart regulates the level of Lmod and how Lmod might be relevant to cardiac muscle disease. In addition, the team is attempting to crystallize Lmod in order to study its structure directly.
University of Pennsylvania School of Medicine
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.
A budding role for a cellular dynamo
Actin, a globular protein found in all eukaryotic cells, is a workhorse that varies remarkably little from baker's yeast to the human body.
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.
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.
More Actin Filaments Current Events and Actin Filaments News Articles
 |
Investigation of Cytoskeletal Systems with Optical Tweezers: Adhesion Forces of Actin Filaments and Malaria Parasites Measured with Optical Tweezers in Microfluidic Environments by Kai Uhrig (Author) Optical tweezers are a versatile tool to apply and measure forces in the piconewton range on microscopic objects that are held by optical forces in a focused laser beam. We employed holographic optical tweezers (HOT) to create extended force sensor arrays, consisting of multiple trapped particles that were controlled and probed individually. The combination of high-speed video microscopy with fluorescence imaging allowed the visualization of labeled protein structures in parallel with the tracking of multiple trapped particles for force measurements. Using this setup, we could perform quantitative force measurements on biological samples with HOT for the first time. This provided the possibility to measure dynamic processes such as the contractility of two-dimensional cross-linked actin... |
|
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. | |
|
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. | |
 |
Mechanism of Myofilament Sliding in Muscle Contraction (Advances in Experimental Medicine and Biology) by Haruo Sugi (Editor), Gerald H. Pollack (Editor) |
| © 2009 BrightSurf.com |