Difference between revisions of "Cytoskeleton - Intermediate Filaments"

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==Lecture Content to be added==
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=Cytoskeleton - Intermediate Filaments=
 +
==Introduction==
 +
[[Image:Intermediate filament organization cartoon.jpg|thumb|Intermediate filament organization]]
 +
[[Image:IF keratin in keratinocytes tem.jpg|thumb|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.
 +
 
 +
== Objectives ==
 +
 
 +
* 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
 +
 
 +
 
 +
== Structure ==
 +
[[Image:Intermediate filament protein dimers cartoon.jpg|300px|Dimer structure]][[Image:IF-vimentin-cartoon.jpg|300px|IF vimentin cartoon]]
 +
[[Image:IF desmin mutants.jpg|300px|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 ===
 +
[[Image:IFfamily.jpg|300px|IF family]]
 +
[[Image:Human keratin genes.jpg|300px|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)
 +
 
 +
Keratins form heterodimers that assemble into heteropolymeric keratin filaments
 +
 
 +
* '''Type III'''
 +
** Desmin (cardiac, skeletal and smooth muscle)
 +
** Vimentin (widespread distribution: leukocytes, blood vessels, endothelial, some epithelial and mesenchymal cells) 56 kDa
 +
** Peripherin (neurons) 57 kDa
 +
** Glial fibrillary acidic protein (GFAP) (astrocytes/glia) 50 kDa
 +
 
 +
Type III intermediate filament proteins can form both homo- and heteropolymeric filaments
 +
 
 +
* '''Type IV'''
 +
** Neurofilament Low NF-L (neurons) 62 kDa
 +
** Neurofilament Medium NF-M (neurons) 110 kDa
 +
** Neurofilament High NF-H (neurons) 130 kDa
 +
 
 +
Neurofilaments form heteropolymers
 +
 
 +
** 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
 +
 
 +
== Function ==
 +
* 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
 +
 
 +
[[Image:Keratin filaments.jpg|300px|Keratin Filaments and Desmosome]]
 +
[[Image:Desmosome1.jpg|300px|Desmosome]]
 +
[[Image:IF desmin plectin cartoon1.jpg|300px|Muscle Desmin]]
 +
 
 +
===Applications===
 +
Take advantage of the unique cell type expression pattern of IF proteins.
 +
* Nestin as a stem cell marker
 +
* GFAP can be used as an astrocyte marker in the analysis of neuronal tissue
 +
* 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.
 +
 
 +
== Abnormalities ==
 +
[[Image:Hutchinson-Gilford Progeria Syndrome.jpg|thumb|Hutchinson-Gilford Progeria Syndrome]]
 +
* Hutchinson–Gilford progeria syndrome - Lamin IF [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176670 OMIM]
 +
* Amyotrophic Lateral Sclerosis (ALS) - NF-H, peripherin [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=105400 OMIM]
 +
* Alexander Disease - GFAP [http://ghr.nlm.nih.gov/condition=alexanderdisease Genetics Home Reference] [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=203450 OMIM]
 +
* Charcot-Marie-Tooth disease - NF-L [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607734 OMIM]
 +
* Parkinson's Disease - NF-L, NF-M [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=168600 OMIM]
 +
* Pachyonychia Congenita [http://ghr.nlm.nih.gov/condition=pachyonychiacongenita Genetics Home Reference]
 +
* Giant Axonal Neuropathy
 +
* Werner syndrome [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=277700 OMIM]
 +
* Desminopathies desmin-related cardio-skeletal myopathy (CSM), also known as desmin-related myopathy (DRM)
 +
** 3 cardiomyopathy forms – dilated, hypertrophic and restrictive cardiomyopathies [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2592258&tool=pmcentrez PMCID: 2592258]
 +
 
 +
'''Inherited Epidermolysis Bullosa''' (EB) [http://www.nlm.nih.gov/medlineplus/ency/article/001457.htm Medline Plus] [http://www.ncbi.nlm.nih.gov/pubmed/18374450 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 [http://ghr.nlm.nih.gov/condition=epidermolysisbullosasimplex Genetics Home Reference]
 +
* Junctional epidermolysis bullosa (JEB) (gene products involved: laminin V, integrin, collagen, not IF related) [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ebj GeneReviews]
 +
* Dominant dystrophic epidermolysis bullosa (DDEB) (a collagen mutation not IF related)
 +
* Recessive dystrophic epidermolysis bullosa (RDEB) (a collagen mutation not IF related)
 +
 
 +
'''Links:''' [http://www.interfil.org Human Intermediate Filament Mutation Database] | [http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/gnd/tocstatic.html Genes and Diseases] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim OMIM - Online Mendelian Inheritance in Man]
 +
 
 +
== History ==
 +
Below are some example historical research finding related to cell junctions from the [http://jcb.rupress.org/misc/fromthearchive.shtml JCB Archive].
 +
 
 +
'''1968''' [http://jcb.rupress.org/cgi/content/full/169/5/704-a] [http://jcb.rupress.org/content/38/3/538.abstract?ijkey=c639df93c1b9c0b1d500f47a4553ee86abbddbda&keytype2=tf_ipsecsha] Not actin, not myosin, but intermediate. They are neither thick nor thin: Howard Holtzer identifies intermediate filaments as a completely new kind of filament.
 +
 
 +
== References ==
 +
 
 +
===Textbooks===
 +
 
 +
====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
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.section.2957#29865 Intermediate Filaments Impart Mechanical Stability to Animal Cells]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.figgrp.2984 Figure 16-16. A model of intermediate filament construction]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.table.2987 Table 16-1.  Major Types of Intermediate Filament Proteins in Vertebrate Cells]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.figgrp.2990 Figure 16-20. Two types of intermediate filaments in cells of the nervous system]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.section.3469#3488 Figure 16-20. Desmosomes Connect Intermediate Filaments from Cell to Cell]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.figgrp.606 Figure 4-9. A cross-sectional view of a typical cell nucleus]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mboc4.figgrp.2174 Figure 12-21. The breakdown and re-formation of the nuclear envelope during mitosis]
 +
 
 +
 
 +
====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 19 Cell Motility and Shape II: Microtubules and Intermediate Filaments
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.section.5543 Intermediate Filaments]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=mcb.figgrp.5550 Figure 19-51. Levels of organization and assembly of intermediate filaments]
 +
 
 +
====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
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.section.1808 Intermediate Filaments]
 +
* [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?db=Books&rid=cooper.section.2265 Signal Transduction and the Cytoskeleton]
 +
 
 +
====Search Online Textbooks====
 +
 
 +
* "intermediate filament" [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=intermediate+filament+mboc4 Molecular Biology of the Cell] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=intermediate+filament+mcb Molecular Cell Biology] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=intermediate+filament+cooper The Cell- A molecular Approach] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=Books&cmd=search&term=intermediate+filament Bookshelf]
 +
 
 +
===IF Database===
 +
 
 +
* [http://www.interfil.org Human Intermediate Filament Database]
 +
 
 +
===Books===
 +
 
 +
* [http://www.amazon.com/Intermediate-Filament-Cytoskeleton-Methods-Biology/dp/0125641737 Intermediate Filament Cytoskeleton, Volume 78 (Methods in Cell Biology) ]
 +
* [http://books.google.com/books?id=6OKS_xx9xTsC Cell Junctions: Adhesion, Development, and Disease‎ by Susan E. La Flamme, Andrew Kowalczyk]
 +
 
 +
===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. [http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed 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. [http://www.ncbi.nlm.nih.gov/sites/entrez?db=PMC 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.  [http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim 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 [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar Entrez]
 +
 
 +
====Search Pubmed====
 +
 
 +
* "intermediate filament"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=intermediate+filament Entrez all databases]
 +
* "lamin"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=lamin Entrez all databases]
 +
* "desmosome"  [http://www.ncbi.nlm.nih.gov/sites/gquery?itool=toolbar&cmd=search&term=desmosome Entrez all databases]
 +
 
 +
====Reviews====
 +
* Intermediate filaments mediate cytoskeletal crosstalk. Chang L, Goldman RD. Nat Rev Mol Cell Biol. 2004 Aug;5(8):601-13. Review. [http://www.ncbi.nlm.nih.gov/pubmed/15366704 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. [http://www.ncbi.nlm.nih.gov/pubmed/17606637 PMID: 17606637]
 +
 
 +
* The desmosome and pemphigus. Waschke J. Histochem Cell Biol. 2008 Jul;130(1):21-54. Epub 2008 Apr 3. Review. [http://www.ncbi.nlm.nih.gov/pubmed/18386043 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. [http://www.ncbi.nlm.nih.gov/pubmed/18178072 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. [http://www.ncbi.nlm.nih.gov/pubmed/18617039 PMID: 18617039]
 +
 
 +
* Oshima RG. Intermediate filaments: a historical perspective. Exp Cell Res. 2007 Jun 10;313(10):1981-94. Epub 2007 Apr 11. Review. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1950476 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. [http://www.ncbi.nlm.nih.gov/pubmed/9438837 PMID: 9438837]
 +
 
 +
====Articles====
 +
 
 +
* 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. [http://www.ncbi.nlm.nih.gov/pubmed/329288 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. [http://www.ncbi.nlm.nih.gov/pubmed/368806 PMID: 368806] [http://www..pnas.org/content/75/10/5034 PNAS]
 +
 
 +
== Acronyms ==
 +
 
 +
'''crescentin'''  bacteria <em>Caulobacter crescentus</em>, with several properties similar to animal IF proteins
 +
 
 +
'''EBS''' epidermolysis bullosa simplex
 +
 
 +
filensin
 +
 
 +
'''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
 +
 
 +
phakinin
 +
 
 +
'''plectin''' an intermediate filament–bound cytolinker protein
 +
 
 +
'''vimentin''' Latin, vimentum for wickerwork or brushwood
 +
 
 +
 
 +
==Images==
 +
 
 +
<gallery>
 +
Image:IF keratin in keratinocytes tem.jpg|IF keratin in keratinocytes (tem)
 +
Image:03lungtem.jpg|lung cell desmosome (tem)
 +
Image:desmosome_tem1.jpg|desmosome (tem)
 +
Image:5pancreas.jpg|pancreas cell desmosome(tem)
 +
Image:Keratin filaments.jpg|Keratin filaments (fl, tem)
 +
Image:Vimentin.jpg|Vimentin (fl)
 +
Image:Hutchinson-Gilford Progeria Syndrome.jpg|Hutchinson-Gilford Progeria Syndrome
 +
Image:Intermediate filament organization cartoon.jpg|Intermediate filament organization
 +
Image:Human keratin genes.jpg|Human keratin genes
 +
Image:Intermediate filament protein dimers cartoon.jpg|Intermediate filament protein dimers cartoon
 +
Image:Desmosome1.jpg|Desmosome
 +
Image:Epidermis structure.jpg|Epidermis structure
 +
Image:Epithelia jns1.jpg|Epithelia junctions
 +
Image:IF desmin plectin cartoon1.jpg|IF desmin plectin cartoon
 +
Image:IF desmin mutants.jpg|IF desmin mutants
 +
Image:IF-vimentin-cartoon.jpg|IF vimentin cartoon
 +
Image:IFfamily.jpg|Image:IF family
 +
</gallery>
 +
 
  
 
{{Template:2011ANAT3231}}
 
{{Template:2011ANAT3231}}

Revision as of 09:48, 4 April 2011

ANAT3231 Cell Biology online lectures from the 2017 course.

Cytoskeleton - Intermediate Filaments

Introduction

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.

Objectives

  • 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


Structure

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)

Keratins form heterodimers that assemble into heteropolymeric keratin filaments

  • Type III
    • Desmin (cardiac, skeletal and smooth muscle)
    • Vimentin (widespread distribution: leukocytes, blood vessels, endothelial, some epithelial and mesenchymal cells) 56 kDa
    • Peripherin (neurons) 57 kDa
    • Glial fibrillary acidic protein (GFAP) (astrocytes/glia) 50 kDa

Type III intermediate filament proteins can form both homo- and heteropolymeric filaments

  • Type IV
    • Neurofilament Low NF-L (neurons) 62 kDa
    • Neurofilament Medium NF-M (neurons) 110 kDa
    • Neurofilament High NF-H (neurons) 130 kDa

Neurofilaments form heteropolymers

    • 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

Function

  • 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

Applications

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

  • Nestin as a stem cell marker
  • GFAP can be used as an astrocyte marker in the analysis of neuronal tissue
  • 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.

Abnormalities

Hutchinson-Gilford Progeria Syndrome
  • Hutchinson–Gilford progeria syndrome - Lamin IF OMIM
  • Amyotrophic Lateral Sclerosis (ALS) - NF-H, peripherin OMIM
  • Alexander Disease - GFAP Genetics Home Reference OMIM
  • Charcot-Marie-Tooth disease - NF-L OMIM
  • Parkinson's Disease - NF-L, NF-M 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) (gene products involved: laminin V, integrin, collagen, not IF related) 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

History

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

1968 [1] [2] Not actin, not myosin, but intermediate. They are neither thick nor thin: Howard Holtzer identifies intermediate filaments as a completely new kind of filament.

References

Textbooks

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

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Reviews

  • 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

Articles

  • 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

Acronyms

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

EBS epidermolysis bullosa simplex

filensin

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

phakinin

plectin an intermediate filament–bound cytolinker protein

vimentin Latin, vimentum for wickerwork or brushwood


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2012 Course Content

Lectures: 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 - Intermediate Filaments | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | 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 | 2012 Revision | Development


Laboratories: Introduction to Lab | Microscopy Methods | Preparation/Fixation | Immunochemistry | Cell Knockout Methods | Cytoskeleton Exercise | Confocal Microscopy | Microarray Visit | Tissue Culture 1 | Tissue Culture 2 | Stem Cells Lab | Stem Cells Analysis



2012 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8 | Group 9

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