Cytoskeleton Introduction
Contents
- 1 Introduction to the Cytoskeleton
- 1.1 Introduction
- 1.2 History Timeline
- 1.3 Selected Paper History
- 1.4 Function
- 1.5 Structure
- 1.6 Many proteins of the cytoskeleton are generated by alternative splicing
- 1.7 Organization
- 1.8 Cytoskeleton Filaments
- 1.9 Prokaryotic Cytoskeleton Filaments
- 1.10 Abnormal
- 1.11 References
- 1.12 2017 Course Content
Introduction to the Cytoskeleton
Please note the link below is to the Guest lecturer slides.
Information shown below is background use only and is not part of the lecture.
Introduction
This lecture will provide an introduction to the 3 filament systems that together form the cell cytoskeleton. Each filament system (microfilaments, intermediate filaments, microtubules) will be the subject of separate lecture which will provide a more detailed coverage in the following 3 lectures. This page contains two resources which explore the history behind the cytoskeleton, Nature Cell Biology milestones and The Journal of Cell Biology archive series. These lists are not complete but give selected examples of key events in the history of the cytoskeleton.
We have introduced the concept of dynamic processes with the eukaryotic cell, but how are these processes of change driven? The cell skeleton, unlike our own rigid skeleton, is the tool by which nearly all dynamic processes take place within the cell and by the whole cell. Key dynamic events of cell shape, surface specializations, cell division, development, adhesion, migration and intracellular transport can all be related to the cell cytoskeleton.
Archive: 2015
History Timeline
- 1942 Discovery of actomyosin
- 1953 Abercrombie’s studies of cell migration
- 1954 Sliding filament model for muscle contraction
- 1965 Dynein, the first microtubule-dependent motor
- 1967 Dynamic filaments in the mitotic spindle
- 1968 Tubulin, the binding partner of colchicine in the mitotic spindle
- 1968–1978 Identification of intermediate filaments
- 1972–1977 Actomyosin contractile ring in cytokinesis
- 1973 Isolation of the first non-conventional myosin
- 1974 Visualization of actin filaments in non-muscle cells
- 1978 Analysis of cytoskeletal dynamics with fluorescently labelled probes
- 1980 Actin-adhesion links to the extracellular matrix
- 1981–1982 Differential interference contrast microscopy
- 1984 Microtubule dynamic instability
- 1985 The microtubule molecular motor kinesin
- 1989 & 1995 g-Tubulin and microtubule-organizing centres
- 1989–1996 Single-molecule assays for motor proteins
- 1990–1993 Structures of actin and myosin
- 1991 Keratins in health and disease
- 1992 Rho GTPases as cytoskeletal regulators
- 1992–1998 Discovery of the bacterial cytoskeleton
- 1993 Cilia and flagella formation and function
- 1994–1998 Isolation of the first actin nucleator
- 1995–1996 Structures of microtubules and kinesin
- 1999 Reconstruction of a complete motile system in vitro
(List from Nature Cytoskeleton Timeline)
Links: Nature Cytoskeleton Milestones | Nature Cytoskeleton Timeline | Nature Cytoskeleton Collection | PDF of all Milestones | Nature Cytoskeleton Library
Selected Paper History
- 1963 Ledbetter and Porter - Microtubules are named, and recognized as a widespread phenomenon even outside of the spindle. JCB Archive
- 1967 Lewis Tilney and Keith Porter - Microtubules shape the cell, find evidence that microtubule polymerization is important for the development and maintenance of cell shape. JCB Archive
- 1968 Borisy and Taylor - The discovery of tubulin, Tubulin is isolated by Gary Borisy and Edwin Taylor as a colchicine-binding activity, and by Ian Gibbon’s group from cilia. Mohri (1968) "gave it the obvious name—the name we considered and rejected." The term "tubulin" was now official, although "spactin," "flactin," and "tektin" stuck around as alternative monikers for a little while (Satir, 1968). JCB Archive
- 1968 Howard Holtzer - Not actin, not myosin, but intermediate, they are neither thick nor thin: Howard Holtzer identifies intermediate filaments as a completely new kind of filament. JCB Archive Ishikawa, H., et al. 1968. J. Cell Biol. 38:538–555
- 1969 Howard Holtzer - Actin in non-muscle cells, research group uses heavy meromyosin as a probe to find actin filaments in non-muscle cells. Holtzer et al. (1972) suggested that there might be more than one type of actin and that each might be associated with a variety of actin-binding proteins in different cell types. Ishikawa, H., et al. 1969. J. Cell Biol. 43:312–328
- 1971 Yamada, Spooner and Wessels - Actin in locomotion, use the newly discovered drug cytochalasin B to show that actin filaments drive cell locomotion. JCB Archive Spooner, B.S., et al. 1971. J. Cell Biol. 49:595–613
- 1980 Heuser - What the cytoskeleton really looks like, combines freeze drying and EM for far more complete view of the cytoskeleton. JCB Archive Heuser, J.E. 1980. J. Cell Biol. 84:560–583
- 1986 Schulze and Kirschner - Microtubules turn over rapidly, chemically labeling microtubules to define their dynamics. JCB Archive Schulze, E., and M. Kirschner. 1986. J. Cell Biol. 102:1020–1031
- 1989 Mitchison - Microtubules get dynamic, photoactivatable tubulin allows the track flux in the spindle. JCB Archive Mitchison, T.J. 1989. J. Cell Biol. 109:637–652
Links: JCB Archive
Function
- functions based upon the filaments physical properties
- each filament system has different properties
- integral strength
- cell shape
- motility
- inside the cell
- whole cell
- motor proteins associated with 2 filament systems
- signal transduction
Note - the Extracellular Matrix has a similar structural role outside of the cell.
Structure
- Network of filamentous proteins
- filaments formed from a few proteins
- monomer protein forms polymer filaments
- located in nucleus and cytoplasmic compartments
- not within organelles
- location based upon cellular function
- named on basis of physical size
Many proteins of the cytoskeleton are generated by alternative splicing
DNA (transcription) -> mRNA Nuclear processing (export)
- DNA -> mRNA splicing (introns removed, exons joined) -> mRNA
- some examples are:
- lamins (nuclear intermediate filaments)
- tau (mictotubule-associated proteins)
- tropomyosins (actin-associated proteins)
Organization
- cytoplasmic
- cortical meshwork under plasma membrane
- three dimensional meshwork through cytoplasm
- nuclear
- cortical meshwork under nuclear envelope
- assembly
- some spontaneous
- assembly sites
- dynamic
- variable stability
- high to low stability
- stability can be altered by associated proteins and signals
- drugs can alter stability
Cytoskeleton Filaments
non-muscle cell cytoskeletons
Microfilaments
- Twisted chain 7 nm diameter
- most abundant protein in cells (5% of all cell protein)
- actin 43 Kd
- Motility
- Adhesion, focal adhesions
- Actin binding proteins
- myosin motors
- Muscle actins
Intermediate Filaments
- different cell types, different intermediate filaments
- all eukaryotes nuclear cytoskeleton the same
- resist stresses applied externally to the cell
- cytoplasmic
- anastomosed network
- flexible intracellular scaffolding
- 10-nanometer diameter
- cross-linking proteins allow interactions with other cytoskeletal networks
- intermediate filament associated proteins (IFAPs)
- coordinate interactions between intermediate filaments and other cytoskeletal elements
and organelles,
- human disorders
- mutations weaken structural framework
- increase the risk of cell rupture
Microtubules
- 25 nm diameter, 14 nm internal channel
- tubulin
- cytoplasmic
- All cells contain
- Same core structure
- Same motors Dynein (-) and Kinesin (+)
- Different associated proteins
- Dynamic
- Continuous remodelling
- Movement
- Intracellular > cellular
- Cell division mitotic spindle
- Specialized structures
- centrosome, basal bodies, Spindle pole
- Cell processes - cilia (9+2)
Prokaryotic Cytoskeleton Filaments
Prokaryotic cells have recently been shown to contain a number of proteins that appear to be analogous to eukaryotic cell cytoskeletal structures and functions. This is still a developing area and is not the focus of this introduction. Discovery of the bacterial cytoskeleton
FtsZ ring
- microtubule homolog
- dynamic and exchanges subunits with the cytoplasmic pool
- assembles into a ring at the future site of bacterial septum in cell division
MreB
- microfilament (actin) homolog
- dynamic and exchanges subunits with the cytoplasmic pool
- assembles into helix-like structures
- thought to spatially restrict cell growth activities during cell elongation
Crescentin
- intermediate filament homolog
- form stable filamentous structures
- continuously incorporate subunits along their length
- grow in a nonpolar fashion
- stably anchored to the cell envelope
Links: Nature Cytoskeleton Milestones 1992–1998 Discovery of the bacterial cytoskeleton
Abnormal
- many mutations associated with human diseases
- toxins can affect organization
- infective bacteria and viruses can be appropriate (use)
References
Textbooks
Essential Cell Biology
- Chapter 16 Cytoskeleton
Molecular Biology of the Cell
Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002
- Molecular Biology of the Cell 4th ed. - IV. Internal Organization of the Cell Chapter 16. The Cytoskeleton
- The Cytoskeleton
Molecular Cell Biology
Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999
- Molecular Cell Biology - Chapter 18. Cell Motility and Shape I: Microfilaments
- Cell Motility and Shape I: Microfilaments
The Cell- A Molecular Approach
Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000
- The Cell - A Molecular Approach - III. Cell Structure and Function Chapter 11 The Cytoskeleton and Cell Movement
- The Cytoskeleton and Cell Movement
- Signal Transduction and the Cytoskeleton
Search Online Textbooks
- "cytoskeleton" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
Books
PubMed
- PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
- PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
- Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
- Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez
Search Pubmed
Jan 2015 search for "cytoskeleton" results in 100,627 papers of which 13,204 are reviews. (2009 - 74,797 papers, 9,672 reviews).
- "cytoskeleton" PubMed reviews | PubMed all articles | PMC reviews | PMC all articles | OMIM | Entrez all databases
Reviews
- Annual Review of Cell and Developmental Biology
- Trends in Cell Biology
- The Vertebrate Primary Cilium in Development, Homeostasis, and Disease
Articles
2017 Course Content
Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cytoskeleton Introduction | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | Cytoskeleton - Intermediate Filaments | Cell Mitochondria | Cell Junctions | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | 2017 Revision
2017 Laboratories: Introduction to Lab | Fixation and Staining |
2017 Projects: Group 1 - Delta | Group 2 - Duct | Group 3 - Beta | Group 4 - Alpha
Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G
