Introduction to the Human Cell

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Danton PhD O'Day. Introduction to the Human Cell

Chapter 1. Introduction

The Unit of Life and Disease

The Cell Inside-Out

The Nucleus and the Human Genome

Amino Acids—Basic Units of Protein Structure

Cell Biological Techniques

Chapter 2. The Human Cell Membrane

Membranes and Biomembranes

The Fluid Mosaic Model of the Cell Membrane

Structure of Phospholipids: The Amphipathic Nature of Phospholipids

Asymmetry of Lipid Bilayer

Micelles: An Alternative Lipid Conformation

Liposomes for Pharmaceutical Delivery

Cholesterol: Stabilizes the Membrane

Membrane Protein Functions

Association of Proteins with the Cell Membrane

Glycoproteins Sugar Coat the Cell

Protein Domains in Cell Membranes

Lipid Rafts and Caveolae

Fluidity of the Cell Membrane: Early Work

Membrane Fluidity: Cell Fusion Experiments

Looking Ahead

Chapter 3. Junctional Adhesion Complexes: Mobile Proteins and Bacterial Mimics

Cell Adhesion Mechanisms

Junctional Adhesion Molecules

Tight Junctions

Tight Junction Proteins: Claudins, Occludins and ZO1

Adherens Junctions

Proteins That Move Between the Nucleus and Junctional Adhesion Complexes

Gastric Ulcers: H. pylori Infection Alters ZO1 Localization

Desmosomes

Desmosomes and Disease

Chapter 4. Gap Junctions: Communication in the Heart and Glands

Gap Junctions

Gap Junction Structure

Gap Junctions and Their Regulation

Connexin Proteins Spontaneously Form Connexons

Gap Junctions and Heart Function

Gap Junctions in Breast Development

Chapter 5. Cell Adhesion Molecules in Normal and Cancer Cells

Two Types of Cell Adhesion

5 Families of Adhesion Molecules

Immunoglobulin Superfamily: N-CAM

Different Forms of N-CAM

Cadherins

Cadherin and the Embryo

Cadherins and Cancer

Integrins

The Extracellular Matrix: A Dynamic Functionary

Integrins and Disease

Selectins

Chapter 6. Signal Transduction and Erectile Dysfunction. What is Signal Transduction?

Conformational Changes in Proteins

Action of Surface Receptors

Classes of Surface Receptor

Ion Channel Receptor

Three Main Types of Enzyme Receptors

cGMP and Erectile Dysfunction (ED)

Cytokine Receptor Superfamily

G Protein-Coupled Receptor (GPCR)

Receptor Diversity

Same Ligand Can Have Different Effects in Different Cells

Different Ligands Can Have Various Effects on Same Effector

Anchoring Proteins Link Components Together

Chapter 7. cAMP Signal Transduction: Sugar Mobilization and Diabetes

The Synthesis and Degradation of cAMP

G Proteins and the G Protein Cycle

cAMP as a Second Messenger

The Human Pancreas

The Regulation of Blood Sugar Levels

The Sugar Wars: Glucagon vs. Insulin

Type 1 and 2 Diabetes

Glucagon and cAMP Signaling in the Liver

cAMP Regulation of PKA

Signal Amplification

Chapter 8. Muscarinic Receptors: From Start to Finish

Muscarinic Acetylcholine Receptors

Signal Transduction via mAchR M1

Phospholipase C: The Production of IP3 and DAG

The Green Mamba: Death and mAchR

Other Phospholipases

The PLA2 Superfamily

Altering Membrane Phospholipids Alters Membrane Attributes

Membrane Phospholipids and Cancer

Protein Kinase C (PKC)

Varying Signaling Components Generates Diversity

Cross-Talk

Terminating Signaling Events

Chapter 9. Calcium and Calmodulin Signaling: Memory and Alzheimer’s Disease. Calcium Sources and Fluxes

Calmodulin (CaM) and Conformational Changes

CaM-Binding Proteins (CaMBPs)

CaM Binding to CaMKII

Pharmacological Antagonism: A Means of Studying Protein Function

Calcium Dysregulation and Alzheimer’s Disease

AD: The Calmodulin Connection

Chapter 10. Motoring Along on Microtubules. Functions of Microtubules

Major Sperm Components and Their Basic Functions

Microtubules in the Sperm Tail

Structure of Microtubules

Cytoskeletal Components: State of Dynamic Equilibrium

Dynamic Equilibrium of Microtubules

Immunolocalization of Microtubules

MTOC: Microtubule-Organizing Centre

Colchicine

MAPs: Microtubule Associated Proteins

Tau and Taupathies

Axonal Transport: Moving Things in Nerve Cells

Tracks for Intracellular Movement

Motor Proteins: Kinesin and Dynein

Electron Microscopy of Purified Motor Proteins

Kinesin and Movement along Microtubules

Vesicle Transport: 2 Directions

Chapter 11. Actin and Myosins, Allergens and Infection

Actin Filaments (F-Actin; Microfilaments)

Effects of Agents on Actin Filaments

Pathogenic Mimicry: Listeria Sneaks into Cells and Uses F-Actin

Hijacking the Actin Cytoskeleton: Listeria Takes Control

Oh No—Not Candida

Actin Accessory Proteins

Actin Interacts with Myosin

Myosin Contraction in Asthma and Allergies

It’s Time for ROCK and Rho

Chapter 12. Cell Movement: Leukocytes and WASPs

Types of Cell Movement

Chemotaxis & Chemoattractants in Humans

Chemokines and Signal Transduction

Leukocytes and Their Movement

Cell Adhesion, Cytoskeleton and Cell Movement

The Integrin-Actin Linkage

Wiskott-Aldrich Syndrome: The WASP proteins

Signaling Events in Leukocyte Chemotaxis

Putting It All Together: The Inflammatory Response

Multistep Adhesion Cascade

Leukocyte Adhesion Deficiency (LAD)

Chapter 13. Biomembrane Fusion: Influenza Virus and HIV Cell Entry

Some Events Involving Biomembrane Fusion

A Multitude of Biomembrane Fusions

Agents That Induce Biomembrane Fusion

Skeletal Muscle Formation: The Fusion of Myoblasts

Retroviruses: Enveloped Viruses

Influenza Virus: pH-Controlled Viral Protein-Mediated Fusion

Model of Biomembrane Fusion: Influenza Virus Fusion Protein

Lipid Bilayer Fusion Induced by Fusogenic Proteins

Human Immunodeficiency Virus (HIV)

HIV Envelope Glycoproteins

The Proteins Involved In HIV Entry

HIV and Immunodeficiency

Chapter 14. Receptor-Mediated Endocytosis: From Hypercholesterolemia to Iron Uptake

Endocytosis

Receptor-Mediated Endocytosis: The Sequence of Events

SEM of Coated Pit

Molecular Model of Clathrin Coat

Adaptor Proteins in Endocytosis

Peptide Signal for Endocytosis

Dynamin Directs Vesicle Separation

Uncoating of Clathrin-Coated Vesicle

Uptake of Cholesterol: The Beginning

Uptake of Cholesterol: From Start to Finish

Receptor-Mediated Endocytosis and Familial Hypercholesterolemia

Iron Uptake

Endocytosis is a Complex Process

Chapter 15. Lysosomes: Death by Enzyme Malfunction

Structure of the Lysosome

Lysosomal Biogenesis: The Formation of Lysosomes

A Cornucopia of Lysosomal Enzymes

Lysosomes and Cell Function

Why Doesn't the Lysosome Digest Itself?

Occupational Diseases: Silicosis

Lysosomes in the Disease Process

Detecting and Correcting Lysosomal Storage Diseases

LROs: Lysosome-Related Organelles

Chapter 16. Protein Targeting and Tay-Sachs Disease. Protein Targeting and Disease

Examples of Protein Targeting

Lysosomal Enzymes: From ER through the Golgi

Lysosomal Enzymes: From Golgi to Lysosome

The CURL Endosome

Recycling Lysosomal Enzymes from the Extracellular Medium

Background to Tay-Sachs Disease: Glycosphingolipids

Tay-Sachs Disease

Tay-Sachs: A Disease of Protein Targeting

I-Cell Disease: The Importance of Lysosomal Enzyme Phosphorylation

Lysosomal Enzyme Targeting: MPR vs. Non-MPR Pathways

Chapter 17. Vesicle Trafficking: COPs, SNARES and Huntington’s Disease

Vesicle Trafficking

COP-Coated Vesicles

Small GTP-Binding Proteins

Vesicle Targeting: The Protein Players

Complementary SNAREs Mediate Vesicle Docking

SNARES: From Vesicle Formation to Docking

The Rab Cycle and Functions

Vesicle Formation, Transport and Fusion at Target Membrane

Docking and Vesicle Fusion

The Complexity of v-SNARE/t-SNARE Interaction

Huntington’s Disease and Vesicular Transport

Chapter 18. The Cell Biology of Cancer

Benign Growths vs. Malignant Tumors

Tissue Culture: Normal vs. Malignant Cells

Changes in Glycoproteins Associated with Cancer

Tumor Development

Metastasis: The Formation of Secondary Tumors

Metastasis: The Sequence of Events

EGFR Signaling and Breast Cancer

EGF Chemotaxis in Breast Cancer Cells

Epidermal Growth Factor Receptor (EGFR)

EGFR Family of Receptor Tyrosine Kinases

EGFR- and Ras-Mediated Signaling

EGFR Signaling: PLCγ Pathway

Co-localization of PKC and EGFR in Cancer Cells

Chapter 19. Apoptosis: Controlling Cell Death

Apoptosis: The Major Events

A Cascade of Caspases Cleaves Proteins

Apoptosis is Induced by the Intrinsic or Extrinsic Pathway

The Intrinsic Pathway: Cell Death Starts Inside

Death Receptors and the Extrinsic Pathway

Apoptosis Signal Transduction

Chapter 20. The Nucleus, Nucleolus and Nucleocytoplasmic Transport

Transport between the Nucleus and Cytoplasm

The Nuclear Pore Complex (NPC)

Different Types of Nucleocytoplasmic Transfer

How Does the NPC Function?

Ran is Required for Receptor-Mediated Nucleocytoplasmic Transfer

Nuclear Localization Signals

Nucleolar Localization Signals (NoLSs)

Appendix I. Some Common Techniques Used in Cell Biology

1. Microscopy

2. Experimental Approaches

Appendix II. SDS-PAGE and Western Blotting. SDS-PAGE

Protein Blotting

Immunodetection

Gel Overlay Techniques

Immunoprecipitation

References

Отрывок из книги

In this book, we’ll cover a diversity of human diseases to increase our understanding of the human cell. Cancer will be examined from a variety of standpoints with foci on cell adhesion and communication as well as cell movement and chemotaxis. Diseases such as Tay-Sachs disease will enlighten us to the critical role of enzymes that at one time were considered to function only during digestion but are now known to be central to cellular and human survival. An analysis of hypercholesterolemia will reveal how molecules selectively enter cells and are subsequently processed through a series of steps that involve carefully regulated movements and fusions of vesicles. Other chapters will look at the cellular basis of bacterial and viral infections and how they use mimicry to infect human cells. These are but a few examples of the novel approach that is taken to understand the role of human cell biology in normal and diseased states.

It has often been said that the cell is the “unit of life.” In other words, anything less than a cell is not considered to be a living creature. The cell is the sole unit that possesses all the criteria that define life. It is able to survive, grow and reproduce on its own. A virus is not considered to be living because it cannot reproduce on its own—it needs to use the machinery present in a living cell to reproduce. The cell is also the “unit of disease” because all human diseases operate at the cellular level. Thus a virus can’t get a disease but it can cause a disease by infecting cells. Unlike viruses, bacteria are cells. Bacteria can also cause human diseases—they do so by infecting cells. Again, this reflects the cell as the basis of disease. This is true for human cells just as it is for the cells of all living creatures. In this book we will look at how the human cell is constructed and, by focusing on specific components and events, understand how it functions. By focusing on a select group of diseases that affect the diverse components and functions of cells further insight will be gained into the normal and abnormal functioning of the human cell.

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Figure 2.7. The basic structure of a typical glycoprotein and its association with the cell membrane.

When the carbohydrate component of the glycoprotein is extensive, typically interacting with extracellular matrix components, it can be seen in the electron microscope. For example, the extensive “sugar coating” of the intestinal epithelium is called the glycocalyx (Figure 2.8). The extensive glycocalyx in the intestine protects against injury, bacterial infections and aids in absorption of nutrients. Some use the term glycocalyx more loosely to mean the surface carbohydrate component of all cells and not just the extensive coating exemplified by intestinal epithelial cells.

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