Cell+Structure+and+Function+II


 * 22 August 2006**
 * Cell Structure and Function II**
 * Dr. Joana Chakraborty, Ph.D.**

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=**Cytoskeleton**=


 * Actin dynamics for membrane extension
 * Can be in globular or filament form
 * Filament networks (bundles) for maintaining cell structure
 * Myosin motors for contractility and vesicle transport
 * Actin bundles and intermediate filaments for cell adhesion
 * Lamin network (intermediate filament) for nuclear structure
 * Inside of nuclear envelope
 * Microtubules work with other cytoskeleton components for proper function

**Actin Filaments and Microfilaments**

 * Structure
 * Thinnest filament, ~6 nm
 * 15% of total protein of a cell
 * G-actin and F-actin types
 * Actin filament has a + and a – end and is dynamic – forming when needed and dissociating when not needed
 * Most material joins on the + end when forming and most material leaves on the – end when dissociating
 * Actin grows fast on + end and very slowly on - end
 * Three classes of actin – α in muscle cells and, β and γ in non-muscle cells
 * Actin-Binding Proteins
 * Necessary for proper function – defects can lead to disease
 * Fimbrin
 * Microvilli, stereocilia, adhesion plaques, yeast actin cables
 * Help actin filaments bind side-by-side to form bundle
 * α- Actinin
 * Filopodia (extension of cell membrane), lamellipodia, stress fibers, adhesion plaques
 * Help actin filaments bind side-by-side to form bundle
 * **[|Spectrin]**
 * Cortical networks
 * Allows cell to retain flexibility necessary for cells such as blood cells to move through the thin corridors of capillary systems
 * Dystrophin
 * Muscle cortical networks
 * Muscular dystrophy occurs when dystrophin is defective
 * Filamin
 * Filopodia, pseudopodia, stress fibers
 * Fascin
 * Filopodia, lamellipodia, stress fibers, microvilli, acrosomal process
 * Villin
 * Microvilli in intestinal and kidney brush border
 * Cofilin
 * Dissociation from – end
 * Severin and Gelsolin
 * Severing, capping + end
 * Mechanism of Assembly and Disassembly
 * Globular actin molecules form a dimer, then a trimer, and continue to polymerize to form the helical actin filament through the nucleation process
 * Rapidly growing and slow growing ends
 * G-actin, Ca2+ and ATP needed
 * Actin Bundles and Filaments – formed by cross-linking proteins
 * Contractile, i.e. cleavage furrow (myosin) – can be used to push things around
 * Gel-like network, i.e. cell cortex (filamin)
 * Parallel, i.e. core of microvilli (villin, fimbrin)
 * Focal contact for cell attachment, i.e. stress fiber (α-actin, talin, vinculin)
 * Microvilli
 * Finger-like projections of surface of intestinal epithelium with variable length (0.5-10 μm)
 * Brush border of intestinal epithelium – increases surface area to transport nutrients by extending plasma membrane using actin filaments
 * Contains core actin filaments, membrane linkage, cross-liked by fimbrin and villin
 * **Action of Drugs**
 * **[|Cytochalasins]** – used to prevent further polymerization of actin by binding to the ends of actin filaments
 * From various fungi
 * **[|Phalloidin]** – binds to actin filaments and stabilizes **against depolymerization**
 * From mushrooms, very potent poison

**Intermediate Filaments**

 * Provide a strong 3-D structural support of cell
 * Kind of like bones of a cell
 * Anchor the nucleus in place
 * Connect the cell membrane and cytoskeleton
 * Form the framework for the maintenance of the nuclear envelope and nuclear structure
 * Structure
 * Two of them join to form a dimer, then two dimmers form a protofilament, elongate, and wrap up into an intermediate filament
 * Principle types of intermediate filament proteins
 * Cytoplasmic Intermediate Filament – can be used to identify the source of cancer primaries
 * [|Keratins] – in epithelial, hair, nails
 * **Desmin** – in muscle cells
 * **Vimentin** – in fibroblast and leukocytes
 * **Glial Fibrillary Acidic Protein** – in astrocytes, Schwann cells
 * **Neurofilaments** – neurons
 * Nuclear Intermediate Filament
 * **Nuclear Lamins** – all nucleated cells
 * Control assembly of nuclear envelop by organizing perinuclear chromatin
 * Type B bines with inner nuclear member
 * Type A and C bind with B
 * Functions
 * Very Stable, distribute tensile strength across cell and tissue
 * No polarity (+ end or – end) because they do not assemble or disassemble easily

**Microtubules**

 * Structure
 * Has a + and – end polarity
 * Types of Microtubules
 * General Cytoplasmic
 * Central pair of cilia and flagella
 * Fused
 * Microtubule Associated Proteins – MAPs
 * Can organized microtubules and affect their stability
 * Assembly and Disassembly of Microtubules
 * Hollow tube composed of 13 protofilaments made from tubulin molecules form to make a microtubule
 * Can be fused in doublets (cilia, flagella) or triplets (basal bodies, centrioles)
 * Have a rapid growing end and slow growing ends
 * Mg2+ and GTP are needed
 * Some MAPs are needed also
 * Formed by α and β tubulin molecules into protofilaments arranged in a cylinder
 * Motor Proteins
 * Kinesin – Transport vesicles to + end
 * Dynein – Transport vesicles to – end
 * Present in cilia and flagella
 * Action of Drugs
 * **[|Colchicine]**, **Colcemid** – inhibit addition of tubulin molecules to microtubules, leading to microtubule depolymerization
 * **[|Vinblastine]**, **Cincristine** – induce the formation of paracrystalline aggregates of tubulin
 * [|Paclitaxel] – Stablizes tubulin

=**Nucleus**=


 * Bound by nuclear envelope, contains nucleolus, chromatin, and nucleoplasm
 * Varying different shapes and sizes
 * Nucleus is the information center of the cell
 * The Interphase Nucleus
 * Distinct nuclear envelope, chromatin (light, filamentous material), nucleoplasm, and some centrosome and centriole (microtubules) structures outside of the nucleus
 * Nuclear Envelope
 * Double lipid bilayer with pore-complexes in envelope
 * Continuous outer membrane with rough ER
 * Inner membrane has nuclear lamin (30-100 nm)
 * Nuclear Pore Complex (NPC)
 * 80-100 nm, composed of proteins called nucleoporins
 * Necessary for precise transport of specific proteins in and out of nucleus
 * Larger molecules must interact with other proteins with nucleoporins for transport
 * Has 3 rings: cytoplasmic, middle, and nucleoplasmic
 * Cytoplasmic and middle rings are connected by 8 spoke-like structures
 * Nucleoplasmic ring has a protruding nuclear basket
 * Middle ring contains a central transporter
 * FG-nucleoporins line the central transporter channel and transport all macromolecules
 * Exportins – transport macromolecules to cytoplasm
 * Importins – transport proteins to nucleus
 * Nucleolus -- **ribosome production factory**
 * Fibrillar center of inactive DNA
 * Pars fibrosa – RNA
 * Pars granulose – maturing ribosomal units
 * Nucleolar matrix – has some nucleolus organization proteins
 * Chromatin – made up of DNA
 * **Hematochromatin**
 * Closer to nuclear envelope and is very dense
 * Not transcriptionally active
 * Low protein synthesis
 * **[|Euchromatin]**
 * Much lighter than hematochromatin
 * Transcriptionally active
 * Meaning euchromatin cells are producing more protein than hematochromatin
 * Centrosome and Centriole
 * [|Centrosome]
 * Microtubular organizing center (MTOC)
 * Some cells may not have centriole but will have centrosome instead
 * Centrosome is composed of the centrioles and surrounding pericentriolar material consisting of γ-tubulin ring complex, pericentrin, and other microtubule-nucleating macromolecules
 * Centrosomes assist in the formation and organization of macrotubules and self-duplication before cell division
 * [|Centriole]
 * Centrioles in the normal in interphase cell are found in pairs at right angles to each other
 * Centrioles are composed of nine triplets of microtubules arranged around a central axis.
 * Centrioles when replicating will separate and bind with tubulin and begin forming microtubules at a right angle
 * Centrioles function in the formation f the centrosome and guide the formation of the spindle apparatus, cilia, and flagella
 * Microtubules (spindle fibers)
 * Kinetochore microtubules – connecting from centrosome to chromosome (“captures” chromosomes)
 * The location where the kinetochore microtubule attaches to the chromosome is called the kinetochore
 * Polar microtubules – from centrosome pole to pole
 * Astral microtubules – from centrosome and extend outwards
 * Microtubules grow outward from the poles

**Mitotic Chromosome Movement**

 * Kinetochore microtubules shorten from – end
 * Motor proteins on polar microtubules push them apart as polar microtubules elongate from + end
 * Astral microtubules shorten from – end while motor proteins also help pull
 * All three actions help separate chromosomes in anaphase
 * The assembly and disassembly of microtubules is what allows the movement of chromosomes (an any other organelles in the cell)
 * Control of assembly and disassembly controlled by availability of Mg2+ and GTP

=**Objectives**=