Cytoskeleton Introduction

From CellBiology


Introduction to the Cytoskeleton

Please note the link below is to the Guest lecturer slides.


2016 Cytoskeleton PPT 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.


"Its not an artefact!"
The first electron micrograph taken of an intact eukaryotic cell from one of Keith Porter's original prints, a montage of five electron micrographs taken on July 6, 1944.


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

Molecular sizes: Myosin, Microtubule, Actin and Collagen


(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
  • 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


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

Cytoskeleton
  • 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
Alternative Splicing of pre-mRNA allows the econding of multiple mRNAs by one single gene.[1]
  • 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

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

Search Online Textbooks

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).

Reviews

Articles



2017 Course Content

Moodle

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