Unit 06 Pt4

Overview of Intermediate Filaments

  • Focus on intermediate filaments as part of the cytoskeleton

  • Present only in some metazoan cells, unlike actin and microtubules which are ubiquitous

  • Diameter: 8-11 nanometers, rope-like structure conferring mechanical strength

Structure and Function

  • Intermediate filaments are important for cellular integrity and stress responses

    • Confers mechanical strength, supporting the structure of epithelial cells

    • Related to nuclear lamins, indicating diversity compared to actins and microtubules

  • Coiled-coil configuration mediated by alpha-helical domains in monomers

  • Formation: Dimers coalesce into antiparallel staggered tetramers

Key Features

  • Lack of nucleotide binding (no GTP or ATP)

  • No polarity in polymerization: no directionality in assembly

  • Up to 32 polypeptides can combine, providing significant tensile strength

  • Can stretch up to three times their length without breaking

Types of Intermediate Filaments

Keratins

  • Most diverse type: dozens of keratin types defined by heterodimeric filament subunits consisting of one acidic and one basic subunit

  • Strong networks formed through disulfide bonds, known as "tough as nails"

  • Certain keratins associated with carcinomas, aiding tissue origin identification in cancers

Epidermolysis Bullosa (EB)

  • A genetic disorder associated with keratin mutations

  • Characterized by skin blistering from minor mechanical stress

  • Result of inadequate tensile strength in intermediate filaments, leading to epithelial cells forming abnormal structures

Neurofilaments

  • Found specifically in neuron tissue, heteropolymers along axons

  • Expression levels affect axon diameter and electrical impulse transmission speed

  • Abnormalities linked with conditions like ALS due to accumulation of neurofilament assemblies

Linker Proteins and Their Functions

  • Example: Plectin connects intermediate filaments to actin and microtubules

  • Important for cellular adhesion and linking structures to the plasma membrane

  • Mutations in linker proteins associated with disorders like EB and muscular dystrophies

Nuclear Lamin Connection

  • SUN and Cache proteins bridge nuclear lamina and cytoskeleton

  • SUN domain proteins located in the inner nuclear membrane; Cache proteins in the outer membrane

  • Interactions facilitate connections between nuclear laminins and other components

  • Mutations can result in progerias and accelerated aging

Septins

  • GTP-binding proteins crucial for cell polarity and division

  • Assemble into nonpolar filaments forming rings and cages

  • Important for compartmentalizing membranes during cell division, migration, and vesicular trafficking

  • Contribute to the formation of primary cilia

  • Visuals included show septin functions in yeast cell division and vesicular transport