BSC 300 Fall 2024_Lecture #21_Nov12_Cell Organization and Movement, Part 2

Lecture Overview

• Lecture #21: Cell Organization and Movement, Part 2

• Major Topics Covered:

  • 18.1 Microtubule Structure and Organization

  • 18.2 Microtubule Dynamics

  • 18.3 Regulation of Microtubule Structure and Dynamics

  • 18.4 Kinesins and Dyneins: Microtubule-Based Motor Proteins

  • 18.5 Cilia and Flagella: Microtubule-Based Surface Structures

  • 18.7 Intermediate Filaments

  • 18.8 Coordination and Cooperation Between Cytoskeletal Elements

Learning Objectives

• Understand traits and functions of various cytoskeletal elements.

• Explore techniques used to study the cytoskeleton.

• Explain dynamic properties of cytoskeletal elements, relating to their construction and function.

• Elucidate the mechanism of molecular motor movement along cytoskeletal elements.

• Describe structures and functions of specific molecular motors (dyneins, kinesins, myosins).

• Understand microtubule organizing centers, their structures and functions.

• Distinguish structures and functions of cilia and flagella, their similarities and differences.

• Clarify the mechanism of muscle contraction at cellular and molecular levels.

• Recognize the existence and importance of non-muscle motility.

Important Concepts on Microtubules

Structure and Organization

• Microtubules are composed of αβ-tubulin, dynamically unstable with polarized ends (+) and (–).

• Nucleation from microtubule organizing centers (MTOCs).

• Structure helps in assembly and hydrolysis of GTP.

Functions of Cytoskeleton

• Provides structural support and maintains cell shape.

• Organizes organelles and directs cellular locomotion.

Properties of Microtubules

• Hollow cylindrical structures made of globular proteins; 13 protofilaments arranged longitudinally.

• Each protofilament consists of dimers of α- and β-tubulin with plus and minus ends.

Tubulin Structure

• Composed of α- and β-tubulin monomers with GTP binding properties.

• α-tubulin: GTP is nonexchangeable; β-tubulin: GDP is exchangeable with GTP.

Types of Microtubules

Singlet, Doublet, and Triplet Structures

• Singlet: 13 protofilaments (most cytoplasmic MTs).

• Doublet: additional wall of 10 protofilaments (found in cilia/flagella).

• Triplet: two additional 10-protofilament walls in centrioles/basal bodies.

Microtubule Assembly

Organization from MTOCs

• MTOCs are specialized structures aiding microtubule nucleation.

• Centrosome: contains centrioles surrounded by pericentriolar material.

Role of γ-Tubulin

• γ-tubulin is crucial for microtubule nucleation at MTOCs, controlling microtubule characteristics.

Microtubule Dynamics

Dynamic Instability

• Microtubules exhibit growth and rapid disassembly, influenced by GTP-cap or GDP-cap.

• Energy from GTP hydrolysis enables microtubules to "search" and capture cellular structures.

Control of Growth/Shrinkage

• GTP-β-tubulin cap stabilizes the microtubule; GDP-β-tubulin leads to rapid disassembly.

Regulation of Microtubule Dynamics

• MAPs stabilizing microtubules, kinseins enhancing catastrophe, and Op18/stathmin destabilizing ends.

Kinesins and Dyneins

Motor Proteins

• Kinesin is a (+) end motor, involved in anterograde transport, while dynein operates at (−) end for retrograde transport.

• Kinesin-1 is processive; one head remains attached while moving.

Kinesin-1 Structure and Function

• Homodimer with heavy chains; ATP hydrolysis powers vesicle transport.

• Regulated by head-to-tail interaction, ensuring high processivity.

Dynein Mechanism

• Cytoplasmic dynein interacts with dynamic cargo via adaptors (dynactin), regulated by nucleotide states.

Cilia and Flagella

Structure and Mechanism

• Composed of an axoneme with a 9+2 arrangement; dynein arms mediate movement.

• Intraflagellar transport is vital for assembly and maintenance.

Role of Calcium Ions

• Movement is regulated by internal calcium concentration; axonemal dynein effectiveness depends on calcium availability.

Intermediate Filaments

General Characteristics

• Composed of various proteins, offering structural stability to cells.

• Lack distinct polarity, and are chemically resistant compared to microtubules.

Classes of IFs

• Five classes with tissue-specific functions; Class V lamins provide structural support to the nucleus.

Nuclear Lamina Structure

• Composed of lamins, essential for organization and rigidity of the nucleus, crucial for chromatin interactions.

Coordination and Cooperation

Interactions Between Elements

• Intermediate filaments connect through adhesion junctions, supporting cross-linking to microtubules for enhanced stability and function.

• Cdc42 protein plays a vital role in orchestrating microtubule and microfilament activities during cell migration.

Summary of Cytoskeletal Components

• Cytoskeleton comprises microtubules, intermediate filaments, and microfilaments, all essential for cellular functionality and structural integrity.

• Microtubules underlay the dynamism of cellular processes, and motor proteins such as kinesins and dyneins facilitate transport and organelle movement along them.