Cytoskeleton II: Microfilaments

Microfilaments

• Microfilaments refer to actin in its polymerized form, with its associated proteins, and are composed of two intertwined strands of actin.
• They help maintain cell shape, allow engulfment events, promote cytoplasmic streaming in plants, and are essential for muscle contraction.
• Microfilaments can be assembled and disassembled within the cell and are used by invading bacteria to move around the cell.

Structure of Actin Monomer and Actin Filament

• Actin subunits have a diameter of 7 nm and are 375 amino acids long.
• Actin filaments have a polarized structure with + and - ends, with the + end extending 5-10 times faster than the - end.

Functions of Microfilaments

• Microfilaments are organized into functional bundles and networks by actin-binding proteins.
• They are especially important in the organization of the plasma membrane, giving shape to surface structures such as microvilli.
• Microfilaments can function on their own or serve as tracks for ATP-powered myosin motor proteins.
• Myosin interacts with actin to cause contraction.
• Microfilaments can assemble into a wide variety of different types of structures within a cell, each underlying particular cellular functions.

Types of Microfilament Structures

• Labile structures: cell cortex, cell adhesion belts, stress fibers, and contractile ring.
• Stable structures: microvillus structure and sarcomere.

Intermediate Filaments

• Intermediate filaments extend throughout the cytoplasm and line the inner nuclear envelope of interphase animal cells.
• They have unique properties that distinguish them from microfilaments and microtubules, including:
  • Biochemical heterogeneity
  • Great tensile strength
  • No intrinsic polarity
  • No known motors that use them as tracks
  • Dynamic in terms of subunit exchange, but more stable than microfilaments and microtubules.

Composition of Intermediate Filaments

• The primary building block of intermediate filaments is a dimer held together through the rod domains, which associate as a coiled coil.
• These dimers associate in an offset fashion to make tetramers, which are assembled end to end and interlocked into long protofilaments.
• Four protofilaments associate into a protofibril, and four protofibrils associate side to side to generate the 10-nm filament.

Classes of Intermediate Filament Proteins

• Class I and II: Keratins are found in animal hair and nails, as well as in cytokeratin filaments that associate with desmosomes in epithelial cells.
• Class III: Vimentin, GFAP, and desmin provide structure and order to muscle Z-disks and restrain smooth muscle from overextension.
• Class IV: Neurofilaments make up class IV and are important for the structure of axons.
• Class V: The lamins are major components of the nuclear lamina and contribute to genome organization as well as to the rigidity of the nucleus.

Coordination and Cooperation Between Cytoskeletal Elements

• Intermediate filaments are linked to specific attachment sites on the plasma membrane and to microfilaments and microtubules.
• Microtubules are used for long-range delivery of organelles, whereas microfilaments handle local delivery.
• The signaling molecule Cdc42 coordinately regulates microfilaments and microtubules during cell migration.

Cell Skeleton Anomalies and Diseases

• Many diseases are associated with defects in intermediate filaments, especially laminopathies, which include a variety of conditions, and mutations in keratin genes, which can cause severe defects in skin.
• Microfilaments irregularities are observed in transformed cells.
• Cancerous cells can be identified by their intermediate filament composition, which can determine the origin of the cancer cells.
• Defective keratins lead to epidermolysis bullosa simplex disorder.