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Cytoskeleton

Cytoskeleton

  • Made up of protein filaments.

  • Important for structure and movement within the cell.

  • All cells have some form of cytoskeleton.

  • Focus on mammalian cells.

Filaments

  • Three types of cytoskeletal filaments

    • Intermediate filaments (intermediate size)

    • Microtubules (largest filaments)

    • Actin filaments (smallest filaments, historically called microfilaments)

  • Intermediate filaments give cells strength and stability against stress (twisting, turning, pulling).

  • Microtubules are involved in the movement of materials, support cell shape, enable movement of structures, and move chromosomes during mitosis.

  • Actin filaments are involved in cell shape, motility, contraction, and cytokinesis.

Intermediate Filaments

  • Strongest cytoskeletal filament.

  • Intermediate in size.

  • Protect cells against stress.

  • Involved in cell-cell junctions (desmosomes).

  • Reinforce the nuclear envelope.

alpha Helical
  • Primarily alpha-helical structure.

  • Form coiled-coil motifs (common in fibrous proteins).

  • Regions closest to n and c terminus are unstructured.

  • Have rope like structures that are like tough rope.

  • Dimeric coil-coil formed by two monomers' alpha helices winding around each other.

Tetramer
  • Two dimeric coil-coils form a tetramer.

  • They are antiparallel (run in opposite directions N to C).

  • Tetramer has overhangs at either end.

Noncolvalent Interactions
  • All interactions besides primary sequence are noncovalent.

  • All of these interactions besides the primary sequence of amino acid, they're all noncovalent interactions.

Bundle of Tetramers
  • Tetramers associate noncovalently to form a bundle of eight tetramers.

  • This comprises 32 monomers.

Assembly
  • Eight tetramers line up and interact noncovalently, creating longer and longer filaments.

  • Intermediate filaments are nonpolar (ends are the same).

  • Are not polar, just because the positive end of one and the negative end of the other cancel out.

  • This structure is a rope-like structure, even though there's lot covalent interactions between these arrays of eight tetramers.

  • If there isn't covalent interactions, you still make a strong interaction.

TEM
  • Spontaneous process and assemble to form structures or grow.

Classes of Intermediate Filaments
  • Different cell types have different intermediate filaments.

  • Coiled-coil domains are conserved across types.

  • Differences primarily in the overhangs.

  • In most cells, one has keratin filaments and are in epithelial cells and mementin also, which is related filaments. These are most connective tissue, blood tissues, muscle cells. nerve cells have a lot of filaments. Nuclear membrane has nuclear lamins that stabilize the structure.

Keratins
  • Present in epithelial cells.

  • 50 different keratin cells exist in the human body.

  • Involved in cell-cell junctions.

  • Secreted by cells (ex: nail bed).

  • Also spread throughout the whole cell.

Neurofilaments
  • Present in nerve cells, especially in axons.

  • Provide structure to the axon.

  • Increased neurofilaments correlate with ALS and neurodegeneration.

  • Bundle will have problems, if we have too many of them for structure.

Nuclear Lamina
  • Located under the nuclear envelope.

  • Offer structure and support to the nuclear envelope.

  • Broken down by phosphorylation during cell division and reassembled by dephosphorylation.

Other Mutation
  • Causes the increase of progeria and rapid aging.

  • Increase problems with cell.

Cytoskeleton Binding Proteins
  • Connect intermediate filaments to other cytoskeletal filaments.

  • Example: plectin (connects microtubules and intermediate filaments).

  • We also have cash domain proteins and sun domain proteins that connect inside and outside of nucleus. It binds to lectin and micro-domain cell within nucleus.

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