A budding role for a cellular dynamo

February 19, 2009

Brandeis 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

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...

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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)

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 & 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.

Selective placement of actin filaments on protein patterned surfaces.
by Lenin J Leon (Author)

Motors proteins are used by living organisms to convert chemical energy into mechanical energy. The human body uses such motors proteins to transport materials through cells and, in the case of the biomolecular motor system of actin and myosin, to contract muscle. By understanding how these biological motors work, artificial motors with improved function may be possible and may be engineered to work in complex biological and non-biological environments. Recent research efforts have focused on understanding how to harness the power of, and manipulate the functioning of biological motors for integration into useful nanoscale systems. One important step towards this integration is the binding of motor proteins onto substrates and the full characterization of the system. The aim of this...

Molecular Interactions of Actin: Actin-Myosin Interaction and Actin-Based Regulation (Results and Problems in Cell Differentiation)
by D.D. Thomas (Editor), C.G. dos Remedios (Editor)

Actin is one of the most widespread proteins in eukaryotic cells. This book and its companion ("Molecular Interactions of Actin. Actin Structure and Actin-Binding Proteins") provide an authoritative and opinionated view of the structure and function of this essential protein. Each section includes an historical perspective and a detailed commentary on actin protein chemistry, molecular and cell biology of actin. While some chapters review the body of knowledge of the subject, others contain new experimental data. This book will appeal to research scientists seeking contemporary overviews of actin-myosin interaction and actin-based regulation. Contributors include senior scientists as well as the new breed of younger scientists.

Mechanism of Myofilament Sliding in Muscle Contraction (Advances in Experimental Medicine and Biology)
by Haruo Sugi (Editor), Gerald H. Pollack (Editor)

Sliding Filament Mechanism in Muscle Contraction: Fifity Years of Research (Advances in Experimental Medicine and Biology)
by Haruo Sugi (Editor)

Sliding Filament Mechanism in Muscle Contraction: Fifty Years of Research covers the history of the sliding filament mechanism in muscle contraction from its discovery in 1954 by H.E. Huxley through and including modern day research. Chapters include topics in dynamic X-ray diffraction, electron microscopy, muscle mechanisms, in-vitro motility assay, cardiac versus smooth muscle, motile systems, and much more.

Actin (Protein Profile)
by Peter Sheterline (Author), Jon Clayton (Author), John Sparrow (Author)

Actins are a highly conserved family of proteins found in virtually all eukaryotic cells. They have prolific roles in cell motility - from the contraction of striated muscle to the movement of organelles within cells, and are known to interact with a diverse number of proteins families from myosins to gelsolins. This up-to-date edition gives a comprehensive account of actin sequence, mutation and structure as well as providing insight into ligand-binding sites and drug and toxin binding. Illustrated throughout, this modern text also contains an extensive bibliography for the interested reader.

Actin: Webster's Timeline History, 2000 - 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 "Actin," including when used in literature (e.g. all authors that might have Actin in their name). As such, this book represents the largest compilation of timeline events associated with Actin 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 sciences (linguistics,...