intermediate filaments

general info about intermediate filaments

• less dynamic structural networks than actin/microtubules

• no polarity or GTP/ATPase activity - subunit exchange rate much lower

• biochemically heterogeneous

• great tensile strength

structure

• head domain at N-terminus

• tail domain at C-terminus

• alpha helical rod domain - 4 alpha helices with linker regions (linker regions give flexibility)

assembly/disassembly of keratin intermediate filaments

• homodimer subunits - rod domains make a coil-coiled structure to give dimer (hydrophobic amino acids are located at specific positions along the alpha-helix that allows dimerisation driven by hydrophobic effect)

• homodimers assemble to form antiparallel tetramer - 2 dimers associate laterally in staggered arrangement with eachother along coil-coiled domain, forms symmetrical structure with no polarity since the dimers have opposite orientations

• tetramers then aggregate into ‘unit length filaments’ - assembled end to end and interlocked to form protofilaments

• 4 protofilaments associate to form a protofibril, 4 protofibrils associate side to side to form a filament

• assembly self-driven since no polarity or ATP/GTPase activity - assembly can still be dynamic

• kinase enzymes phosphorylate intermediate filaments and bring about disassembly

major classes of protofilaments

• class I and II:

acid/basic keratins - found in epithelia

intermediate keratin filaments join cells in epithelial sheets - provide tissue strength and integrity

• class III:

desmin, GFAP, vimentin

found in cells of mesodermal origin (muscle, glial cells, mesenchymal cells)

involved in sarcomere organisation, integrity

• class IV:

neurofilaments - found in neurons

involved in axon organisation

• class V:

lamins - maintain integrity of nuclear envelope since line nuclei of all animal tissues, phosphorylated during mitosis/meiosis, releasing phosphorylated dimers into cytoplasm and allowing spindle formation

example - intermediate filaments joining cells in epithelial sheets

• keratin filaments associate with desmosomes and hemidesmosomes in epithelia - hold sheets together

• when mutated, the epidermis blisters since there is detachment of epithelia and unstable cellular structures - leads to very fragile and damaged skin with no structural integrity