Cytoskeleton Flashcards
What is the cytoskeleton?
• Network of filaments in the cytosol
• All filaments bind a target; link organelles
to each other and to the PM
• Composed of 3 main types of filaments:
• Microfilaments—whole-cell movement,
muscle contraction, cell shape, cytokinesis
• Intermediate filaments—strength
• Microtubules—movement of cilia and
flagella, intracellular trafficking, mitotic
spindle formation
Actin is a central component of microfilaments
• Actin present in all cells but
different isoforms predominate in
various cell types
• G-actin monomers polymerise →
F-actin microfilament
Functions of Actin
Forms structural and motility
systems:
• Helps maintain cell shape
• cf. spectrin
• Provides structural support for
plasma membranes (eg.
dystrophin), including
protrusions (eg. microvilli)
Functions of Actin
Restricts diffusion of organelles
• At the cell cortex, actin network excludes
organelles
• Provides anchor for cell adhesion
molecules
• Contraction (cf. myosin)
• Muscle cells
• During telophase of mitosis, actomyosin
contractile ring forms
Cells migrate along extracellular matrix via actin
Necessary during embryogenesis, movement of axons in response to growth factors, movement of white blood cells toward site of infection, phagocytosis • Leading edge temporarily attaches to extracellular matrix
What are Thin Filaments?
Name given to actin, especially in muscle cells • Composed mainly of F -actin • Tropomyosin • Troponin complex (skeletal, cardiac cells) • TnI • TnC • TnT
Myosin
Thick filament • Actin-binding, motor protein • Binds ATP • Found in muscle, non-muscle cells. • Different isoforms exist
Intermediate Filaments
Diameter of microtubules > IF > microfilaments • Impart mechanical strength to resist mechanical forces placed on cell • Eg. Fluid sheer stress in blood vessels; stress in contracting skeletal muscles • Subunits are heterogeneous • No ATP nor GTP required for polymerization • No polarity • Major IFs: keratins, vimentins (incl. desmin), neurofilaments, lamins, nestin
Epithelial IFs form strong attachment sites at cell surface
• Keratins are IFs found in cytosol of epithelial cells • Interconnect desmosomes in neighbouring cells to help stabilize epithelial sheets • Desmosome: adhesive junction that helps keep adjacent cells joined together • Associated with strong adhesion between epithelial cells and underlying ECM
Neurofilaments
Neurofilaments in nerve cell axon serve as structural support to resist breakage • Extend along length of axon
Microtubules (green), intermediate filaments (purple) and actin filaments (red).
Vimentin, Desmin
Vimentin family of proteins includes desmin and vimentin • Vimentin found in mesoderm-derived cells. Widely distributed in the body • Desmin expressed in all types of muscle cells • Important for stabilizing the contractile apparatus
Lamins
Lamins found exclusively in all nuclei: lamins A, B, C are part of nuclear lamina • Line inner nuclear surface, protecting chromatin from damage due to mechanical stress • Disassemble at start of mitosis • Re-form lamina at end of mitosis
Nestin
Expressed widely: neural progenitor cells, many other cell types • Associated with cell proliferation
Microtubules
Cytosolic, hollow, polar cylinders made of αand β-tubulin heterodimers
- Functions include: motility (cilia and flagella), chromosomal movements during cell division (mitosis, meiosis), transport of intracellular vesicles
- Can rapidly assemble and disassemble
- Can re-direct traffic in a cell by disassembling m’tubules in one region and assembling in another
Assembly of Microtubules
• α- and β-tubulin subunits each have bound GTP during assembly • Add to plus end • Rapidly assemble, disassemble • For mitosis, m’tubules disassemble, reassemble to form mitotic spindle, then disassemble for chromosomal separation
Assembly of Microtubules
• Centrosome composed of 2 centrioles plus pericentriolar material • Centrosome complex caps minus end during elongation of m’tubule
Dynamic instability—Growth and breakdown of microtubules
Assembly then catastrophic breakdown of m’tubules = dynamic instability • Minus end capped at centrosome complex • Tubulin subunits, each with bound GTP, add to plus end • β-tubulin GTP hydrolysed to GDP. (αtubulin always maintains its GTP) • Presence of GTP at + end encourages faster assembly • For elongation, GTP-tubulin addition must occur faster than nucleotide hydrolysis
Dynamic instability—Growth and shrinkage of microtubules
• Disassembly occurs from plus end • Capping plus end (microtubule capping proteins) prevents disassembly
Vesicle and Organelle Transport
Movement of intracellular vesicles, secretory vesicles, organelles, etc. • Transport requires energy (ATP) • M’tubule motor proteins (ATPases) needed • Kinesin, kinesin-related proteins— anterograde transport • Cytoplasmic dynein—retrograde transport
Movement of Cilia and Flagella —Axoneme
Cilia found in respiratory tract lining (clear mucus), lining of oviduct (transport eggs to uterus) • Flagellum allows sperm to swim • Axoneme: 9+2 arrangement of m’tubules extending from basal body, anchored in plasma membrane • Axonemal dynein (an ATPase) needed for motility • Axoneme composed of m’tubules and other proteins to allow ‘whipping’ of cilia and wave -like motion of flagella • These m’tubules are stable; resist breakdown
Dynamics in Mitosis
• In interphase, • Centrosome is replicated • M’tubules disassemble • New centrosomes form poles of spindle • M’tubules orient spindle for cell division • M’tubules growing from each centrosome attach chromatids to spindle poles • Transports chromosomes to poles during anaphase
A 39-year-old man presents with progressive weakness in the muscles of his lower limbs. Investigations reveal a mutation in the gene coding for desmin. Which of the following would be most directly affected in these muscle cells of the patient?
A) Breakdown of nuclear membrane B) Maintenance of structural support C) Movement of acetylcholine-containing vesicles D) Movement of cilia E) Movement of entire cell
Which of the following is most effective in promoting polymerization of the cytoskeletal filament important for the movement of a white blood cell?
A) Cross-linking of actin with myosin B) Interaction of keratin with GTP C) Interaction of tubulin with GTP D) Phosphorylation of ADP bound to actin E) Phosphorylation of lamins
A 15-year-old male is brought to the physician because of shortness of breath during a sporting activity. He was diagnosed with cystic fibrosis at 3 months of age. Which of the following describes the most likely route or mechanism by which normal copies of the affected protein would be transported to their final destination?
A) Along polymers of tubulin B) Along vimentin filaments C) Binding to importin at nuclear pores D) Through activity of flagella E) Through activity of cilia F) Via axonemal dynein
