Receptor Biology

Michael S. Roberts, Anne E. Kruchten

• Publisher: Wiley-VCH
• Year: 2016
• ISBN:
  9783527800179
• Edition: 1
• Topic: Biowissenschaften
• Subtopic: Zellbiologie

This book is geared to every student in biology, pharmacy and medicine who needs to become familiar with receptor mediated signaling. The text starts with explaining some basics in membrane biochemistry, hormone biology and the concept of receptor based signaling as the main form of communication between cells and of cells with the environment. It goes on covering each receptor superfamily in detail including their structure and evolutionary context. The last part focusses exclusively on examples where thorough knowledge of receptors is critical: pharmaceutical research, developmental biology, neurobiology and evolutionary biology. Richly illustrated, the book is perfectly suited for all courses covering receptor based signaling, regardless whether they are part of the biology, medicine or pharmacology program.

Part I
Introduction

Chapter 1
Introduction

The beauty of reductionism is that it gives you something to do next.

Steve Jones [1]

Biological processes require communication between cells and between individuals. In all kinds of living organisms, this communication begins at the molecular level. Small signaling molecules (proteins, amino acids, steroids, and other substances) are the messages that pass from one cell to the next; large protein receptors are the receivers of the message. Receptors bind the smaller molecules much as a lock receives a key or a glove receives a hand [2]. Other proteins in the cell membrane associated with the receptors convey the message to the interior of the cell.

Very few biochemical or physiological functions in our bodies are not somehow touched by these molecules or by the process of cellular communication. Here are some examples of how receptors are involved in a variety of biological processes:

• Sperm and egg meet, recognize each other, and bind by a receptor mechanism.
• Embryos develop by cell communication: one cell releases a hormone that binds to a receptor on another cell, and the second cell changes its shape and function, initiating the process of differentiation.
• Hormone-like neurotransmitters are released from one cell (a nerve) and bind to receptors on the surface of a nearby cell (another nerve or a muscle) to cause thought or movement.
• The digestive system propels food and releases enzymes according to the binding of hormones to cells lining the digestive tract.
• Immune system cells contain on their surfaces receptors that are able to recognize foreign proteins and attack invading cells.
• Diseases often act by subverting normal receptor function.

This introductory chapter covers general concepts of communication and how chemical communication compares with human communication; how evolution applies to receptor molecules; and how a pure chemical entity such as a receptor can initiate such large-scale functions as thought.

1.1 Receptors and Signaling

1.1.1 General Aspects of Signaling

Signaling is the means by which a cell knows what is happening in its surroundings, and is also the method by which one cell instructs nearby cells to alter their behavior. Organismal cell signaling involves molecular interactions, but the biological mechanisms of signaling are analogous to the ones humans use for verbal communication.

1.1.2 Verbal and Physiological Signals

Any sort of signaling requires that the sender and receiver are capable of interpreting the signals in the same way [3]:

• The sender must relay a characteristic signal, and it must be received by a characteristic device;
• The signal is arbitrary: it bears no real relation to the process it starts but is simply a way of obtaining a response in the receiver;
• The signal is simpler than the process it sets in motion.

These rules are easily understood in terms of human communication:

• The signals are the words of the language, and the receiver is the hearing/thinking/acting apparatus of another person;
• Each language uses different words, yet all people can express the same thoughts.
• Any word (e.g., HELP) evokes in its hearer a set of thoughts or behaviors that are much more complex than the word itself.

The units of cellular communication abide by these same rules:

• The correct signal is the drug or hormone, the correct receiver is the cell surface receptor or nuclear receptor.
• It is arbitrary that one amino acid (e.g., glutamic acid) is an excitatory transmitter in the nervous system, whereas another amino acid (e.g., glycine) is an inhibitory transmitter.
• The binding of a single transmitter molecule to its receptor is adequate to start a cascade of intracellular events that amplifies the signal into a complex biochemical response.

In addition to these constraints, three more generally apply to biological communication:

• The receptor must be present on the correct tissue, it must be selective or specific to the hormone, and the receptor must not be present in tissues where the response is not desired; thus, the timing of the message must be coordinated with the presence of the receptor for that message.
• The signal must always mean the same thing to a particular receptor–effector mechanism.
• Some transmitters act on more than one type of receptor, often activating antagonistic cellular processes.

The analogies drawn between human communication and chemical communication are symbolic, yet the correspondence between the two systems is being strengthened as we find more instances where human interactions are being found to be at least partly chemical (e.g., the importance of pheromone-like substances in human behavior [4]).

1.1.3 Criteria for Recognizing Transmitters and Receptors

This book refers to signaling molecules in several ways. The most general term is ligand, which means any molecule that binds to a receptor. A ligand that activates its receptor is called an agonist. Hormones, transmitters, and pheromones are all agonists, and are naturally produced by organisms for signaling.

1.1.4 Agonists

The substances that serve as agonists are often also important as metabolic molecules within the cell. Thus, simply showing that a cell produces acetylcholine, for example, does not demonstrate its role as a transmitter. For a substance to be accepted as a specific transmitter or hormone, it must be shown to: [5]

• be synthesized, stored, and released from the proper type of cell (e.g., neuron or endocrine cell);
• have a specific mechanism for removal from the extracellular space near the target cell;
• be effective as an agonist if added to the target cell by experimenters.

1.1.5 Receptors

Cells can be activated by processes other than receptor mechanisms. To be accepted as a receptor mechanism, a process must be shown to [6]

• be activated by one or only a few substances;
• bind these substances with high affinity;
• be able to transmit the binding event to the cell interior.

These criteria for identifying receptors are not just for convenience; each has its basis in receptor structure, and later chapters show how these criteria are derived from, and actually define, the molecular mechanisms by which receptors operate.

1.1.6 Receptor–Enzyme Similarities

Enzymes are familiar proteins: they have active sites at which small substrate molecules bind and are converted to products. The relation between a receptor and its agonist is quite similar, at least at the binding step, to the action of enzymes: the receptor binds the agonist with high affinity because of the match between the shape and electric charge distribution of both molecules. The act of binding alters the shape of the receptor at another location; this change in shape is transmitted to other cellular proteins, thus stimulating further cellular processes.

As useful as the enzyme analogy is, however, enzyme action is unlike the receptor mechanism in some ways:

• A receptor-binding event has no “product” because the agonist is unaltered by its interaction with the receptor.
• The receptor–agonist complex has an additional role after binding: the conversion of the binding signal to an intracellular event, such as enzyme activation or gene transcription.

Enzymes are important intracellular biochemical regulators; receptors are important regulators at the interface of the cell. Because of this location, they have a crucial role as molecular guardians, controlling the initial encounters between cells and chemicals in their environments.

1.2 Types of Receptors and Hormones

1.2.1 R...

Table of contents

• Cover
• Title Page
• Copyright
• Dedication
• Table of Contents
• Acknowledgments
• Part I: Introduction
• Part II: Fundamentals
• Part III: Receptor Types and Function
• Part IV: Applications
• Glossary
• References
• Index
• End User License Agreement