Cellular Biology I: The Cytoskeleton

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Questions and Answers

What is the role of the base of the primary cilium?

It initiates cell division.

It generates electrical signals.

It provides a diffusion barrier for membrane proteins. (correct)

It stores genetic material.

How is the primary cilium related to cell signaling?

It acts as a passive receptor for signals.

It produces signals independently of cellular conditions.

It conveys both mechanical and chemical signals to regulate cellular behavior. (correct)

It only responds to chemical signals.

Which statement best describes the expression of the primary cilium during the cell cycle?

It is lost during G0 phase of the cell cycle. (correct)

It is dismantled during interphase.

It is present in all phases of the cell cycle.

It is only present during mitosis.

What is one of the main functions of intermediate filaments in the cell?

They confer mechanical resistance and form a cage-like network. Signup and view all the answers

What characterizes the composition of intermediate filaments?

They consist of more than 70 different proteins classified into five categories. Signup and view all the answers

What are the primary components of the cytoskeleton in eukaryotic cells?

Microtubules, Intermediate filaments, Microfilaments Signup and view all the answers

Which function does microtubules NOT perform within eukaryotic cells?

Cellular respiration Signup and view all the answers

How do microtubules respond to cellular demands?

They can rapidly grow or shrink in size. Signup and view all the answers

What is the role of microtubules in cilia and flagella?

They form the axial shaft known as the axoneme. Signup and view all the answers

What is NOT a characteristic of microtubules?

They are interconnected by covalent bonds. Signup and view all the answers

Which of the following is a function of the cytoskeleton?

Organelles’ positioning within the cell Signup and view all the answers

During cell division, microtubules primarily function as part of which structure?

Mitotic spindle Signup and view all the answers

What is the diameter of a microtubule?

25 nm Signup and view all the answers

What structure forms the wall of a microtubule?

13 protofilaments Signup and view all the answers

What occurs at the + end of a microtubule during dynamics?

Dimer addition exceeds removal Signup and view all the answers

What happens to tubulin-GDP dimers during microtubule growth?

They cause instability Signup and view all the answers

What is the purpose of microtubule-associated proteins (MAPs)?

To contribute to microtubule assembly and function Signup and view all the answers

What triggers the catastrophic shortening of a microtubule?

Absence of new GTP dimers Signup and view all the answers

What modification affects the binding of MAPs to microtubules?

Ser-Thr phosphorylation Signup and view all the answers

How do microtubules exhibit dynamic instability?

They grow and shorten at different rates Signup and view all the answers

What type of proteins form transverse bridges among microtubules?

Microtubule-associated proteins (MAPs) Signup and view all the answers

What happens to the Tau protein in Alzheimer’s disease?

It becomes hyperphosphorylated and forms neurofibrillary tangles Signup and view all the answers

Which proteins are responsible for transporting cargo along microtubules?

Kinesins and dyneins Signup and view all the answers

What characterizes the movement of kinesins along microtubules?

They employ a ‘hand-over-hand’ mechanism and move towards the plus end Signup and view all the answers

What is the primary energy source for the movement of kinesins and dyneins?

ATP hydrolysis Signup and view all the answers

Which statement accurately describes dynein motor proteins?

They are large heteropolymeric proteins with identical heavy chains Signup and view all the answers

How does the interaction between the two heads of kinesins enhance their function?

When one head binds, it causes the other head to move forward in a coordinated manner Signup and view all the answers

Why is Tau protein considered an important factor in neuronal degeneration in Alzheimer's disease?

Hyperphosphorylated Tau fails to bind microtubules, leading to cell damage Signup and view all the answers

What structural feature is characteristic of kinesins?

They consist of tetramers with two globular heads and a fan-shaped tail Signup and view all the answers

Which of the following best describes the directionality of kinesins and dyneins in their function?

Kinesins move towards the plus end while dyneins move towards the minus end Signup and view all the answers

What is the primary structural organization of the axoneme?

9+2 microtubule arrangement with a central pair Signup and view all the answers

What do motor proteins like kinesins and dyneins facilitate in cilia and flagella?

Bidirectional transport along the axoneme Signup and view all the answers

What is the primary function of the primary cilium?

Acts as a sensory organelle for mechanotransduction Signup and view all the answers

How are the peripheral doublets of the axoneme connected?

Through interdoublet nexin bridges Signup and view all the answers

Which characteristic differentiates primary cilia from motile cilia?

Function as cellular antennae Signup and view all the answers

What component does the axoneme lack in primary cilia compared to motile cilia?

Central pair of microtubules Signup and view all the answers

Which of the following best describes the role of radial spokes in cilia and flagella?

Facilitate the sliding of microtubules Signup and view all the answers

What discovery is attributed to Karl Zimmerman regarding primary cilia?

They act as cellular antennae Signup and view all the answers

What essential process is mediated by motor proteins in flagellar motility?

Conformational changes to modify microtubule angles Signup and view all the answers

In what way does intraflagellar transport (IFT) function in cilia and flagella?

Enables the transport of proteins along the axoneme Signup and view all the answers

Study Notes

Cytoskeleton

The cytoskeleton is a 3D network found in all eukaryotic cells.
It's formed by microtubules, intermediate filaments, and microfilaments.
These components are interconnected by non-covalent bonds
The cytoskeleton structure is highly dynamic, meaning it rapidly assembles and disassembles.

The Cytoskeleton (Details)

Microtubules:
Polymer: αβ-tubulin heterodimers
Diameter: Outer 25 nm, Inner 15 nm
Functions: Organization and maintenance of cell shape, chromosome movements, intracellular transport, and cell motility.
Microfilaments:
- Polymer: G-actin monomers
- Diameter: 7 nm
- Functions: Muscle contraction, cell locomotion, cytoplasmic streaming, cytokinesis, and maintenance of animal cell shape.
Intermediate Filaments:
- Polymer: Various proteins
- Diameter: 8-12 nm
- Functions: Structural support, maintenance of cell shape, formation of nuclear lamina, and strengthening of nerve cell axons.

Functional Facts

Mechanical and structural support
Organelle positioning
Movement and transport of intracellular cargo
Cellular motility and contractility
Cellular division

Microtubules

Microtubules are important components of the cytoskeleton in all eukaryotic cells.
They support the cytoplasm, form the mitotic spindle during cell division, and are central to cilia and flagella.
Microtubules act as tracks for the movement of macromolecules and other subcellular structures.
They are dynamic structures, capable of rapidly growing or shrinking.
Made up of polymers of α/β tubulin
Have a hollow tubular structure.
Consist of 13 protofilaments.
Polarized: Plus (+β) end and Minus (-α) end.

Microtubules: Overview

Microtubules have extremely dynamic structures.
They can rapidly grow or shrink depending on the number of tubulin molecules they contain.

Microtubules: Structure

Tubular, hollow, and non-branched structures.
Polymers of α/β tubulin.
External diameter is 25nm, and wall thickness is 4 nm
Wall is formed by 13 protofilaments.
Subunits tubulin α/β heterodimers confer polarity.

Microtubule Dynamics

Microtubules are polarized.
Tubulin subunits are added to the plus end and removed from the minus end.
The entire microtubule wall is built through a continuous renewal process ("treadmilling").

Microtubule Dynamic Instability

Microtubule ends can grow or shrink at different rates.
The rate of growth at the plus end is often faster than removal.
The rate of growth at the minus end is slower than removal.
Microtubule dynamics occur based on GTP-dependent dynamic equilibrium
Microtubule growth occurs when the subunits incorporated at the end are GTP bound.

Microtubule Dynamic Instability: The Structural Cap Model

GTP-bound tubulin dimers at the plus end form a structural cap.
Loss of GTP from tubulin causes tension at the minus end that releases when GTP dimers are lacking.
This process leads to "catastrophic shortening".

Microtubules' Associated Proteins (MAPs)

Heterogeneous group of proteins.
Take part in microtubule assembly.
They're anchored to the microtubule wall while some extend outside.
Form transverse bridges among microtubules.
They contribute to multiple functions like microtubule stability or in transport mechanisms.

Microtubules' Associated Proteins (MAPs): Regulation

The binding of MAPs to microtubules is regulated by Ser-Thr phosphorylation.
MAP phosphorylation leads to detachment, resulting in microtubule instability and disruption.

Prolongation Neuronal

Tau protein is an important MAP, but in Alzheimer's disease, tau proteins get overly phosphorylated causing a disruption in microtubules.

Microtubule Motor Proteins: Kinesins and Dyneins

Convert chemical energy (ATP hydrolysis) into mechanical energy (conformational changes).
Transport cargoes along microtubule trails.
The cargoes include macromolecules, vesicles, mitochondria, lysosomes, chromosomes, and cytoskeletal fractions.
Move along a unidirectional path.

Kinesins

Superfamily of related proteins (kinesin-related proteins).
Tetramers have heavy and light chains
Two globular heads for binding microtubules and hydrolyzing ATP
A neck forming a stalk, and a tail for binding cargo.
Move along microtubules towards the plus end.
Use a hand-over-hand mechanism.

Microtubules Motor Proteins: Dyneins

Huge heteropolymeric protein with two heavy chains and other intermediate and light chains.
Have a stalk and a head with microtubule-binding sites.
The head is the force-generating engine.
Movement is towards the minus end.

Microtubule-Organizing Centers (MTOCs)

Structures that anchor the minus ends of microtubules.
Centrosomes: usually adjacent to the nucleus.
Basal bodies: below the plasma membrane.
These structures are critical for microtubule assembly.

Centrosomes

Main site for microtubule initiation in animal cells
Control the number and polarity of microtubules, the number of protofilaments in their walls, and the time and location of their assembly

Basal Bodies

Site of microtubule nucleation at the base of cilia and flagella.
Have a similar structure to centrioles.

Microtubule Biogenesis

Nucleation: Interaction among y- and β-tubulin. Assembly of a starting nucleus. Stabilization of bonds between subunits.
Elongation: Addition of new subunits and rapid progressive polymerization.

Cilia and Flagella

Structures elongating from the cell surface, having a cytoskeletal shaft (axoneme).
Motile cilia displace cells or substances/particles and move in a perpendicular direction.
Flagella move as a wave, pushing cells forward and move in a parallel direction.

Axoneme

Series of parallel microtubules.
9 + 2 microtubule organization: nine peripheral doublets of A+B microtubules linked by interdoublet nexin bridges, and one central pair of microtubules.
Wrapped by a sheath and connected to peripheral doublets by radial spokes.

Intraflagellar Transport (IFT)

Motor proteins (kinesins and dyneins) for bidirectional transport along the axoneme.

Cilia and Flagellar Motility

Motor proteins (kinesins and dyneins) mediate conformational changes that dynamically modify the angles of inclinations by causing microtubules to slide over one another

Primary Cilia

Non-motile cellular antennae.
Capture mechanical stimuli and transduce them inside the cell as a molecular cascade mechanotransduction
Part of the cell signaling pathways.

The Primary Cilium

Microtubule-based, non-motile organelle.
Extends from basal body, receiving and processing molecular and mechanical signals.
Discovered by Karl Zimmerman and named by Sergei Sorokin.

The Primary Cilium: Structural Facts

Axoneme: derived from the centrosomal mother centriole; lacks the central doublet.
Ciliary membrane continuous with the plasma membrane. Unique in composition.

The Primary Cilium: Structural Facts (Details)

Basal body: modified centriole where the axoneme extension starts.
Transition fibres (TF): mediate docking of the basal body to the plasma membrane.
Transition zone (TZ): contains specialized gating structures that regulate the entrance and exit of ciliary proteins

The Primary Cilium: Structural Assembly and Maintenance

Ciliary assembly and maintenance depend on vesicular transport from the Golgi network to the periciliary membrane.
Vesicles are incorporated into the periciliary membrane, sometimes via lateral transport or trans-membrane diffusion.
Intraflagellar transport (IFT) mediates the docking and fusion of vesicles on the mother centriole for axoneme extension.

The Primary Cilium: Structural Facts (Additional Details)

Cilioplasm: a highly compartmentalized intracellular environment.
The base of the cilium is a membrane diffusion barrier. Prevents lateral protein diffusion between plasma and ciliary membranes that are related to cell signaling, including cell proliferation, migration, and interaction with the ECM.
Ciliary trafficking is regulated by the BBSome, a multi-protein complex.

The Primary Cilium: Functions

A multifunctional antenna.
Involved in apicobasal and planar cell polarity (PCP) maintenance.
Senses mechanical/chemical changes.
Involved in conveying signaling information to regulate cell proliferation, migration, and interactions with the ECM.
Multiple interconnected signaling pathways like Sonic Hedgehog (SHH), Transforming Growth Factor (TGFβ), and Wnt
Important for various cellular processes.

Primary Cilium Functions (Regulation)

Primary cilium expression is tightly regulated during the cell cycle.
Cilium dismantles during mitosis, and centrioles duplicate to form spindle poles
Cilium is temporarily resorbed before S phase
Cilium is typically lost during G0 as quiescent cells cease to sense and signal environmental cues.

The Primary Cilium: Role in Development

During the brain's development, the integrity of the ciliary signaling is needed for:
- Radial glia progenitor migration
- Cortical scaffolding
- Neuroblast orientation
- Neuronal migration
- Correct cortical patterning

The Primary Cilium: Role in Craniofacial Malformations

Defects in ciliary signaling and basal body proteins cause ciliopathies.
Ciliopathies impact different tissues and cells due to pleiotropy

Intermediate Filaments

Fibrous, non-polarized, non-branched filaments, with a diameter of 10-12 nanometers.
Spread throughout the cytoskeleton, providing mechanical resilience.
Less sensitive to chemical agents than other cytoskeletal elements (more difficult to solubilize).

Intermediate Filaments: Composition

70 different proteins form subunits.
Classified into 5 categories:
- I-IV cytoplasmic
- V nuclear

Intermediate Filaments: Structure (Tetramer)

Basic unit: tetramer formed by two homodimers of two polypeptides.
The a-helical rods align parallel to form a coiled coil dimer,
Subsequently to a protofibril tetramer,
8 tetramers associate laterally to form larger filaments, called intermediate filaments, of~ 60 nm length.
No chemical energy for the assembly needed.
Important structural role to reinforce the cytoskeleton.

Intermediate Filaments: Function

Scaffold for cellular architecture.
Maintain cellular shape of neurons.
Connect to the plasma membrane, microtubules, and microfilaments.
Key to absorbing mechanical stress.

Type III Intermediate Filaments (Example)

Vimentin, Desmin, GFAP, and Peripherin

Type IV Intermediate Filaments (Example)

Neurofilament proteins: NF-L, NF-M, and NF-H

Type V Intermediate Filaments (Example)

Lamin A and Lamin B form the nuclear lamina.

Microfilaments

Composed of globular actin (G-actin) subunits.
Polymerize into a flexible, branched filamentous actin (F-actin)
8 nm in diameter and polarized.
Functions: Cellular motility, intracellular movements, phagocytosis, and cytokinesis.
Regulated by ATP, which changes conformation in G-actin.

Microfilaments: Assembly-Disassembly

ATP-actin monomers are added to the plus end and removed from the minus end depending on the concentration of ATP, with a critical concentration threshold.

Myosins: The Microfilaments’ Motor Protein

Motor proteins that interact with microfilaments.
Humans contain about 40 different myosins.
Two general categories: Conventional (type II) myosins, found in muscle tissue, and unconventional myosins (type I and III-XVIII).

Myosins: Features

Typically symmetrical structure/ heteroexamer: 6 polypeptides chains (heavy and light chains).
The heads bind F-actin and have similar structure while the tails are highly divergent.

Myosin Subunits: Bipolar Filament Formation

Myosin subunits form a bipolar filament shape.
Tails are towards the center and heads are towards the opposite ends.
Heads generate forces to pull two F-actin filaments toward each other, which is the basic mechanism for muscle contraction.

Muscle Contraction

Muscle contractions are coordinated by alterations of calcium concentration with regulatory proteins like troponin and tropomyosin.

Dystrophin and DAPC

Dystrophin: rod-shaped protein.
Interacts with other proteins (a-dystrobrevin, syncoilin, synemin, sarcoglycans, dystroglycan, and sarcospan) to form the Dystrophin-Associated Protein Complex (DAPC)
Links the cytoskeleton of muscle fibers to the extracellular matrix (ECM)
N-terminal binds to F-actin, C-terminal binds to the DAPC at the sarcolemma.

Dystrophin and Muscle Dystrophy

Dystrophin, encoded by the DMD gene, largest gene in the human genome
Mutations lead to Muscular Dystrophies (XLR): Duchenne and Becker
Loss/reduction of Dystrophin leads to DAPC destabilization, progressive fiber damage, and membrane leakage.
DMD patients often become wheelchair-bound by 12 years old.

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Description

Explore the intricacies of the cytoskeleton in eukaryotic cells in this first part of the Cellular Biology course. Learn about the structure and dynamics of microtubules, intermediate filaments, and microfilaments. Engage with key concepts to enhance your understanding of cellular biology.