2009 Lecture 10

From CellBiology

Cytoskeleton - Intermediate Filaments


Intermediate filament organization
IF keratin in keratinocytes (tem)

This lecture introduces the intermediate filaments, their structure and function within the cell. Unlike the microfilament and microtubule systems, the filaments themselves consist of a wide variety of different proteins. These intermediate filaments have important structural roles in cell integrity both internally and through specialized cellular junctions that occur between cell-cell and cell-matrix which surrounds them. This topic will be addressed again when we look at the cell cytoskeleton and the extracellular matrix.

Dr Mark Hill (2009)

Lecture Audio

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Lecture 10: Cytoskeleton Intermediate Filaments Lecture Date: 08-04-2009 Lecture Time: 10:00 Venue: BioMed E Speaker: Mark Hill


  • Broad understanding of the cell cytoskeleton
  • Understanding of intermediate filament function
  • Understanding of intermediate filament structure
  • Understanding of intermediate filament proteins
  • Understanding of intermediate filament location in nucleus and cytoplasm
  • Understanding of intermediate filament adhesion junctions
  • Broad understanding of intermediate filament abnormalities


Dimer structureIF vimentin cartoon desmin EM

Physical Characteristics

  • 10 nm diameter
  • Named by size relative to other cytoskeletal filaments
  • intermediate filaments have no structural polarity
  • Monomer - central α-helical domain
  • Dimer - 2 monomers form parallel coiled coil
  • Tetramer - pair of parallel dimers associates in an antiparallel staggered fashion
    • tetramer is the soluble subunit (analogous to MT αβ-tubulin dimer, or MF actin monomer)
  • Provide rope-like resistance to mechanical stress
  • In muscle- link Z discs of adjacent myofibrils
  • Organization can be altered by phosphorylation

IF Types

IF family Human keratin genes

  • Type I (n = 28)
    • Acidic keratins (pI < 5.7) 40–64 kDa
      • K9-28 (epithelia)
      • K31-40 (hair/nail)
  • Type II (n = 26)
    • Basic keratins (pI ≥ 6.0) 53–67 kDa
      • K1-8, K71-80 (epithelia)
      • K81-86 (hair/nail)
  • Type III
    • Desmin (cardiac, skeletal and smooth muscle)
    • Vimentin (mesenchymal) 56 kDa
    • Peripherin (neurons) 57 kDa
    • Glial fibrillary acidic protein (GFAP) (astrocytes/glia) 50 kDa
    • Neurofilament Low NF-L (neurons) 62 kDa
    • Neurofilament Medium NF-M (neurons) 110 kDa
    • Neurofilament High NF-H (neurons) 130 kDa
  • Type IV
    • α-internexin (CNS neurons)
    • Synemins (muscle)
    • Syncoilin (muscle)
    • Nestin (stem cell marker) 220 kDa
  • Type V
    • Lamin A/C (ubiquitous) 62–72 kDa
    • Lamin B1/2 (ubiquitous) 65–68 kDa
  • Orphan
    • Phakinin (lens)
    • Filensin (lens)

Intermediate Filament Associated Protein (IFAP)

  • Cross-link intermediate filaments with one another
    • forming a bundle (also called a tonofilament) or a network
  • IFAPs
    • Plectin 500 kDa Striated muscle, epithelia Nuclear envelop
    • Syncoilin 64 kDa Striated muscle
    • Nesprin-3 117 kDa Kerotinocytes
    • Paranemin 280 kDa
    • Desmuslin 230 kDa Synemin?


  • found in some metazoans (vertebrates, nematodes, and molluscs)
  • Desmin interacts with nebulin linking intermediate filament network and sarcomeres at the Z-discs
  • Keratin filament formation originates mainly from sites close to the actin-rich cell cortex
  • 2 alternate theories as to IF load/strain transmission
    • entropic gels - where no individual intermediate filaments experiences direct loading in tension
    • single intermediate filaments and bundles - extensible and elastic in vitro, and therefore well-suited to bearing tensional loads

Keratin Filaments and Desmosome Desmosome Muscle Desmin


Take advantage of the unique cell type expression pattern of IF proteins.

  • Nestin as a stem cell marker
  • Vimentin antibody can be used as a neural stem cell marker (ab45939)
  • Vimentin is highly expressed in fibroblasts and some expression in T- and B-lymphocytes. Expressed in many hormone-independent mammary carcinoma cell lines.


Hutchinson-Gilford Progeria Syndrome
  • Hutchinson–Gilford progeria syndrome - Lamin IF OMIM
  • Alexander Disease Genetics Home Reference OMIM
  • Pachyonychia Congenita Genetics Home Reference
  • Giant Axonal Neuropathy
  • Werner syndrome OMIM
  • Desminopathies desmin-related cardio-skeletal myopathy (CSM), also known as desmin-related myopathy (DRM)
    • 3 cardiomyopathy forms – dilated, hypertrophic and restrictive cardiomyopathies PMCID: 2592258

Inherited Epidermolysis Bullosa (EB) Medline Plus EB classification

  • Is characterized by a marked mechanical fragility of epithelial tissues and the formation of blisters, erosions and poorly healing skin ulcers.

Represents four major groups of skin diseases:

  • Epidermolysis Bullosa Simplex (EBS) - mutations in KRT14 and KRT5 genes Genetics Home Reference
  • Junctional epidermolysis bullosa (JEB) GeneReviews
  • Dominant dystrophic epidermolysis bullosa (DDEB) (a collagen mutation not IF related)
  • Recessive dystrophic epidermolysis bullosa (RDEB) (a collagen mutation not IF related)

Links: Human Intermediate Filament Mutation Database | Genes and Diseases | OMIM - Online Mendelian Inheritance in Man


Below are some example historical research finding related to cell junctions from the JCB Archive.

1968 Not actin, not myosin, but intermediate They are neither thick nor thin: Howard Holtzer identifies intermediate filaments as a completely new kind of filament.



Essential Cell Biology

  • Chapter 19 Tissues Epithelial sheets and Cell-Cell Junctions p606

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 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



  • 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


  • Intermediate filaments mediate cytoskeletal crosstalk. Chang L, Goldman RD. Nat Rev Mol Cell Biol. 2004 Aug;5(8):601-13. Review. PMID: 15366704
  • Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. Kim S, Coulombe PA. Genes Dev. 2007 Jul 1;21(13):1581-97. Review. PMID: 17606637
  • The desmosome and pemphigus. Waschke J. Histochem Cell Biol. 2008 Jul;130(1):21-54. Epub 2008 Apr 3. Review. PMID: 18386043
  • Intermediate filaments: versatile building blocks of cell structure Goldman RD, Grin B, Mendez MG, Kuczmarski ER. Curr Opin Cell Biol. 2008 Feb;20(1):28-34. Epub 2008 Jan 4. Review. PMID: 18178072
  • Electron microscopy of intermediate filaments: teaming up with atomic force and confocal laser scanning microscopy. Kreplak L, Richter K, Aebi U, Herrmann H. Methods Cell Biol. 2008;88:273-97. Review. PMID: 18617039
  • Oshima RG. Intermediate filaments: a historical perspective. Exp Cell Res. 2007 Jun 10;313(10):1981-94. Epub 2007 Apr 11. Review. PMID: 17493611
  • Fuchs E, Cleveland DW. A structural scaffolding of intermediate filaments in health and disease. Science. 1998 Jan 23;279(5350):514-9. Review. PMID: 9438837


  • Visualization of a system of filaments 7-10 nm thick in cultured cells of an epithelioid line (Pt K2) by immunofluorescence microscopy. Osborn M, Franke WW, Weber K. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2490-4. PMID: 329288
  • Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Franke WW, Schmid E, Osborn M, Weber K. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5034-8. PMID: 368806 PNAS


crescentin bacteria Caulobacter crescentus, with several properties similar to animal IF proteins

EBS epidermolysis bullosa simplex


GFAP glial gibrillary acidic protein

IF Intermediate Filament

IFAP Intermediate Filament Associated Protein

IFP Intermediate Filament Protein

KF Keratin filament

LMNA lamin A gene

NF neurofilament

NF-L neurofilament-low molecular mass protein

NF-M neurofilament-medium molecular mass protein

NF-H neurofilament-high molecular mass protein


plectin an intermediate filament–bound cytolinker protein

vimentin Latin, vimentum for wickerwork or brushwood


2009 Course Content


Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cell Mitochondria | Cell Junctions | Cytoskeleton Introduction | Cytoskeleton 1 Intermediate Filaments | Cytoskeleton 2 Microtubules | Cytoskeleton 3 Microfilaments | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells | Stem Cells | Development | Revision


Introduction to Lab | Microscopy Methods | Preparation/Fixation | Immunochemistry | Cell Knockout Methods | Cytoskeleton Exercise | Confocal Microscopy | Tissue Culture 1 | Tissue Culture 2 | Microarray Lab visit

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G