Cell Structure and Function Lecture 14

Cytoskeleton

A network of interconnected filaments and tubules extending through the cytosol, involved in cell movement and division.

Microfilaments

The smallest of the cytoskeletal filaments, composed of actin subunits, involved in muscle contraction, cell migration, and cytoplasmic streaming.

Microtubules

Cylindrical structures composed of tubulin subunits, about 25 nm in diameter, involved in various cellular functions including movement.

G-actin

Globular actin monomers that bind to ATP or ADP and can polymerize into F-actin.

F-actin

Filamentous actin formed by the polymerization of G-actin monomers, with a helical structure.

Polarity of Microfilaments

Microfilaments have distinct plus (barbed) and minus (pointed) ends, influencing their growth and depolymerization.

Actin-Binding Proteins

Proteins that regulate the polymerization, length, and organization of actin filaments.

Rho GTPases

A family of monomeric G proteins that regulate the cytoskeleton, influencing the formation of stress fibers, lamellipodia, and filopodia.

Dynamic Instability

The phenomenon whereby microtubules undergo rapid transitions between growth and shrinkage.

Microtubule-Organizing Center (MTOC)

A structure where microtubules are organized and anchored, commonly a centrosome in animal cells.

Tau

A microtubule-associated protein that stabilizes microtubules and is implicated in Alzheimer's disease when dysregulated.

Centriole Structure

Cylindrical structures composed of microtubules that help organize the mitotic spindle during cell division.

Formins

Proteins that promote the growth of long actin filaments, functioning independently of the Arp2/3 complex.

Nucleotide Hydrolysis

The process by which ATP bound to actin is hydrolyzed after incorporation into microfilaments, affecting their stability.

Intermediate Filaments

Cytoskeletal components approximately 10 nm in diameter, providing mechanical strength and structural support to cells, and are highly diverse.

Kinesin

A motor protein that moves along microtubules, typically towards the plus end (anterograde transport), carrying vesicles and organelles.

Dynein

A motor protein that moves along microtubules, typically towards the minus end (retrograde transport), involved in vesicle transport and ciliary/flagellar movement.

Myosin

A motor protein that interacts with actin filaments to facilitate muscle contraction, cell movement, and intracellular transport.

Arp2/3 Complex

A protein complex that initiates the formation of branched actin networks, crucial for lamellipodia formation and cell motility.

Cilia and Flagella

Hair-like cellular appendages composed of microtubules, involved in cell motility (e.g., sperm flagella) or moving fluids over surfaces (e.g., tracheal cilia).

Keratin

A type of intermediate filament found in epithelial cells, providing structural integrity to skin, hair, and nails.

General Functions of the Cytoskeleton

Provides structural support, maintains cell shape, enables cell movement, facilitates intracellular transport, and plays a role in cell division.

Three Main Components of the Cytoskeleton

Microfilaments (actin filaments), intermediate filaments, and microtubules.

Diameter of Microfilaments

Approximately 6-8 nm in diameter.

Actin Polymerization

The process by which G-actin monomers, typically ATP-bound, assemble head-to-tail to form F-actin filaments.

Actin Depolymerization

The process by which F-actin filaments disassemble into G-actin monomers, often occurring at the minus end after ATP hydrolysis.

Critical Concentration (Actin)

The concentration of free G-actin monomers in the cytosol at which the rate of polymerization is equal to the rate of depolymerization.

Treadmilling (Actin)

A phenomenon in actin filaments where polymerization occurs preferentially at the plus end while depolymerization occurs at the minus end, creating a net movement of subunits through the filament.

Role of ATP Hydrolysis in Actin Filaments

After G-actin monomers are incorporated into F-actin, their bound ATP is hydrolyzed to ADP, reducing the stability of the filament, particularly at the minus end.

Microfilament Plus End

The rapidly growing end of an actin filament, often referred to as the 'barbed' end, where ATP-G-actin preferentially adds.

Microfilament Minus End

The slowly growing or 'pointed' end of an actin filament, where ADP-G-actin tends to dissociate.

Capping Proteins (Actin)

Proteins that bind to the ends of actin filaments to prevent further polymerization or depolymerization, thereby regulating filament length.

Severing Proteins (Actin)

Proteins that bind to and sever actin filaments, breaking them into shorter pieces and increasing the number of free ends available for polymerization.

Bundling Proteins (Actin)

Proteins that cross-link actin filaments into parallel arrays, forming structures like microvilli or filopodia.

GTPase Rac

A Rho GTPase involved in regulating the formation of lamellipodia and membrane ruffles, promoting branched actin networks.

GTPase Cdc42

A Rho GTPase involved in regulating the formation of filopodia and establishing cell polarity, promoting unbranched actin growth.

GTPase RhoA

A Rho GTPase involved in regulating the formation of stress fibers and focal adhesions, promoting contractile actin bundles.

Lamellipodia

Broad, sheet-like protrusions of the cell's plasma membrane, driven by branched actin networks, that enable cell crawling.

Filopodia

Thin, stiff, finger-like protrusions of the cell's plasma membrane, containing parallel bundles of actin filaments, used for cellular exploration and sensing.

Stress Fibers

Contractile bundles of actin filaments and myosin II that anchor the cell to the substrate via focal adhesions, providing mechanical tension.

Tubulin Subunits

Microtubules are composed of alpha-tubulin and beta-tubulin, which form heterodimers.

Alpha-Tubulin

One of the two protein subunits of a tubulin dimer; it binds GTP but does not hydrolyze it.

Beta-Tubulin

The other protein subunit of a tubulin dimer; it binds GTP and can hydrolyze it to GDP.

Tubulin Dimers

The basic structural unit of microtubules, consisting of one alpha-tubulin and one beta-tubulin protein, which can polymerize end-to-end.

Protofilaments

Linear chains of alternating alpha- and beta-tubulin subunits, typically 13 of which associate laterally to form the cylindrical wall of a microtubule.

Microtubule Polarity

Microtubules exhibit intrinsic polarity with a distinct plus end (beta-tubulin exposed) and a minus end (alpha-tubulin exposed).

GTP Hydrolysis in Microtubules

GTP bound to beta-tubulin is hydrolyzed to GDP shortly after the tubulin dimer is incorporated into a microtubule, affecting filament stability.

GTP Cap (Microtubules)

A region of GTP-bound tubulin dimers at the plus end of a growing microtubule, which stabilizes the filament and promotes continued growth.

Catastrophe (Microtubules)

A rapid transition of a microtubule from a growing state to a shrinking state, typically caused by the loss of the GTP cap.

Rescue (Microtubules)

The transition of a shrinking microtubule back to a growing state, often initiated by the re-establishment of a GTP cap.

Microtubule Plus End

The fast-growing end of a microtubule (capped by beta-tubulin), typically oriented away from the Microtubule-Organizing Center (MTOC).

Microtubule Minus End

The slow-growing end of a microtubule (capped by alpha-tubulin), typically anchored in the Microtubule-Organizing Center (MTOC).

Gamma-Tubulin Ring Complex ($\gamma$-TuRC)

A complex of proteins containing gamma-tubulin, located in the pericentriolar material of MTOCs, which nucleates (initiates the formation of) new microtubules.

Centrosome

The primary Microtubule-Organizing Center (MTOC) in animal cells, typically comprising two centrioles arranged perpendicularly and surrounded by pericentriolar material.

Pericentriolar Material

The amorphous, electron-dense matrix surrounding the centrioles in an animal cell centrosome, containing gamma-tubulin ring complexes and other proteins essential for microtubule nucleation.

Basal Bodies

Structures identical in form to centrioles (nine triplet microtubules) that are located at the base of cilia and flagella and serve as their organizing centers.

Roles of Kinesin

Kinesins are motor proteins primarily responsible for anterograde transport (movement towards the plus end) of vesicles, organelles, and macromolecules along microtubules.

Roles of Dynein

Dyneins are motor proteins primarily involved in retrograde transport (movement towards the minus end) of cargo along microtubules, and in the beating of cilia and flagella.

Directionality of Kinesin

Most kinesin motors move toward the plus end of microtubules.

Directionality of Dynein

Dynein motors move toward the minus end of microtubules.

MAPs (Microtubule-Associated Proteins)

A diverse group of proteins that bind to microtubules, regulating their stability, assembly, spacing, and interactions with other cellular components.

Microtubules in Cilia and Flagella

Cilia and flagella contain a highly organized arrangement of microtubules called the axoneme, typically in a '9+2' pattern (nine doublet microtubules surrounding two central singlets).

Axoneme

The central cytoskeletal core of a cilium or flagellum, composed of an organized array of microtubules and associated proteins responsible for their movement.

Lack of Polarity (Intermediate Filaments)

Unlike microfilaments and microtubules, intermediate filaments do not have distinct polarized ends (plus or minus) and exhibit no Treadmilling or dynamic instability.

Intermediate Filament Assembly

Monomers form coiled-coil dimers, which then align in an antiparallel, staggered fashion to form tetramers, which then associate laterally to form the final filamentous structure.

Intermediate Filament Monomer

The basic polypeptide chain of an intermediate filament, characterized by a central alpha-helical rod domain flanked by globular head and tail domains.

Intermediate Filament Dimer

Two intermediate filament monomers wound around each other in a coiled-coil structure.

Intermediate Filament Tetramer

Two intermediate filament dimers associating in a staggered, antiparallel fashion.

Vimentin

A type of intermediate filament predominantly found in mesenchymal cells (e.g., fibroblasts, endothelial cells), providing mechanical support.

Neurofilaments

Intermediate filaments found specifically in neurons, providing structural support to axons and determining their diameter, which influences signal conduction speed.

Lamins

Intermediate filaments that form a meshwork (nuclear lamina) on the inner surface of the nuclear envelope, providing structural support to the nucleus and organizing chromatin.

Primary Function of Intermediate Filaments

To provide mechanical strength, resisting stretching and compression, thereby increasing the overall durability of the cell and tissue.

Desmosomes

Specialized cell junctions that provide strong cell-to-cell adhesion by anchoring intermediate filaments of adjacent cells to a dense plaque in the plasma membrane.

Hemidesmosomes

Specialized cell junctions that anchor the intermediate filaments within a cell to the extracellular matrix, providing strong cell-to-matrix adhesion.

Actomyosin Contraction

The process driven by the interaction of actin filaments and myosin motor proteins, primarily responsible for muscle contraction, cytokinesis, and cell motility.

Energy Source for Motor Proteins

ATP hydrolysis provides the energy for the conformational changes that allow motor proteins like kinesin, dynein, and myosin to move along their respective tracks.

Profilin

An actin-binding protein that promotes the exchange of bound ADP for ATP on G-actin, thus stimulating actin polymerization, especially at the plus end.

Cofilin

An actin-binding protein that severs ADP-containing actin filaments, primarily promoting depolymerization from the minus end and increasing the number of free ends for polymerization or depolymerization.

Thymosin β4

An actin-binding protein that sequesters G-actin monomers, preventing their polymerization into F-actin filaments and maintaining a pool of free actin for rapid assembly.

Guanine Nucleotide Exchange Factors (GEFs) (Rho GTPases)

Proteins that activate Rho GTPases by catalyzing the exchange of GDP for GTP, switching the GTPase to an active, signal-transducing state.

GTPase-Activating Proteins (GAPs) (Rho GTPases)

Proteins that inactivate Rho GTPases by stimulating their intrinsic GTP hydrolysis activity, converting bound GTP to GDP and returning the GTPase to an inactive state.

Kinesin-1

Also known as conventional kinesin, it is a highly processive motor protein that moves along microtubules towards the plus end, crucial for the long-distance transport of vesicles and organelles.

Cytoplasmic Dynein 1

The primary form of dynein in animal cells, responsible for retrograde transport along microtubules (towards the minus end) of various cellular cargo, and positioning of organelles like the Golgi apparatus and endoplasmic reticulum.

Mitotic Spindle

A bipolar structure composed of microtubules and associated proteins that forms during cell division to segregate chromosomes equally into daughter cells.

Actin Nucleation

The rate-limiting initial step in actin filament formation where a small, stable nucleus of actin monomers is formed, typically facilitated by nucleating proteins like Arp2/3 complex or formins.

Microtubule Severing Proteins (e.g., Katanin)

Enzymatic proteins that actively cut microtubules into shorter fragments, which can lead to rapid depolymerization or rearrangement of the microtubule display.

Contractile Ring (Cytokinesis)

A structure formed by actin filaments and myosin II that constricts the cell during cytokinesis, dividing the cytoplasm after nuclear division.

Actin Nucleation Sites

Specific regions within the cell where new actin filaments are initiated, often controlled by proteins such as the Arp2/3 complex (for branched networks) or formins (for unbranched filaments).

Microtubule Stability vs. Lability

Microtubules can exhibit varying degrees of stability; some are highly dynamic and undergo rapid growth/shrinkage (labile), while others are more stable (e.g., in cilia), a balance regulated by various Microtubule-Associated Proteins (MAPs) and post-translational modifications.

Motor Protein 'Walking' Mechanism

Motor proteins move along their respective tracks (actin or microtubules) by an ATP-hydrolysis-driven cycle of binding, conformational change, and detachment, resulting in directional movement.

Nuclear Lamina Assembly/Disassembly

The dynamic polymerization and depolymerization of intermediate filament lamins, predominantly regulated by phosphorylation and dephosphorylation events, which is critical for the breakdown and re-formation of the nuclear envelope during mitosis.