The Intermediate Filaments

Dr. Ferran Valderrama

fvalderr@sgul.ac.uk
Intermediate Filaments

 Structure

 Polymerization

 IF types

 Intermediate Filaments
Binding proteins (IFBP)

 Function

2 Dr Ferran Valderrama - Biomedical Sciences - SGUL

Structure of the intermediate filaments

• Toughest of the cytoskeletal filaments

(resistant to detergents, high salt etc).
• Ropelike with many long strands
twisted together and made up of
different subunits.
• Intermediate size (8-12nm) between
actin and microtubules.
• Form a network:
– Throughout the cytoplasm, joining up
to cell-cell junctions (desmosomes).
• Withstands mechanical stress when
cells are stretched.
– And surrounding nucleus
• Strengthens the nuclear envelope.
3 Dr Ferran Valderrama - Biomedical Sciences - SGUL
 Intermediate filaments polymerization

• Each unit is made of:

– N-terminal globular
head
– C-terminal globular tail
– Central elongated rod-
like domain
• Units form stable
dimers
• Every 2 dimers form a
tetramear
• Tetramers bind to each
other and twist to
constitute a rope-like
filament 4 Dr Ferran Valderrama - Biomedical Sciences - SGUL
 Types of Intermediate Filaments

• According to the protein units they are made of and

their localization:

5 Dr Ferran Valderrama - Biomedical Sciences - SGUL

Intermediate Filaments Binding Proteins (IFBP)
• Mainly linkers of IF structures.
• IFBP stabilize and reinforce IF into 3D networks
• Examples:
– Fillagrin:
• binds keratin filaments into bundles.
– Synamin and Plectin:
• bind desmin and vimentin
• Link IF to the other cytoskeleton compounds (i.e. actin and
microtubules) as well as to cell-cell contact structures
(desmosomes).
– Plakins:
• Keep the contact between desmosomes of epithelial cells.
6 Dr Ferran Valderrama - Biomedical Sciences - SGUL
Functions of the Intermediate Filaments in
the cytoplasm
• In the cytoplasm they provide:
– Tensile strength: this enable the cells to
withstand mechanical stress (to stretch!)
– Structural support by:
• Creating a deformable 3D structural framework
• Reinforcing cell shape and fix organelle localization

7 Dr Ferran Valderrama - Biomedical Sciences - SGUL

 Functions of the Intermediate Filaments in
the nucleus
• present in all nucleated eukaryotic
cells
• form mesh rather than “rope-like”
structure
• line in the inner face of the nuclear
envelope to:
– strengthen it
– provide attachment sites for chromatin
• disassemble and reform at each cell
division as nuclear envelope
disintegrates
– i.e. very different from the stable
cytoplasmic IFs
– process controlled by post-
translational modifications (mainly
phosphorylation and
dephosphorylation) 8 Dr Ferran Valderrama - Biomedical Sciences - SGUL
The Intermediate Filaments

Dr. Ferran Valderrama

fvalderr@sgul.ac.uk