Cell Signaling: Different forms of Cell Signaling, Types of Signal Molecules and Signal Receptors

Environment that we live on is constantly changing. In order to survive an organism need to adapt and make necessary adjustments in accordance with the changing environment.¹This is accomplished through well-developed cell-cell communication system which includes hormone-receptor interactions, a host of genes and their products, i.e. proteins. There also exist a number of signal molecules and their metabolites which make use of various signaling pathways. Cell internal communication as well as communication with the external environment is essential for survival of an organism.

Signal transduction

Signal transduction, simply, refers to conversion of a signal from one form to another. When target cell receives stimulus from the environment, it propagates and responds to information. This process is known as signaling. A signaling cells releases extracellular signaling molecules which bind to the receptor protein of the appropriate target cell. The receptor protein transforms the signal into an intracellular message.¹Various additional proteins and small molecules participate in the propagation of the signal to its ultimate destination in a cell. As the signal reaches its final destination, it evokes an appropriate cellular response.

Phases of Signal transduction

Cell signaling basically involves three main stages which are:

Reception
Transduction
Response

Reception

A signaling molecule binds to a receptor protein in target cell. The target cell detects the presence of signaling molecule through their binding with the receptors.

Transduction

It involves a step or a sequence of changes required to propagate the signal to its ultimate destination and induce cellular response. When a signaling molecule binds to the receptor, it causes conformational changes in receptor protein.¹ The transformed protein molecule interacts with the cytosolic molecules known as secondary messengers which in turn starts a series of chain reactions ultimately leading to the target gene or protein expression. Some signal molecules may directly activate target gene or protein without any involvement of secondary messengers. (E.g. steroid)

Response

Response is the cellular changes that occurs due to the signal. It might be in the form of change in the enzyme activity, or three dimensional structure of protein, which ultimately affects the metabolism of the cell.

Signal molecule

Signal molecules are the molecules responsible for transmitting information between the cells. The shape, size and function of different signaling molecules may vary greatly from one another. A single cell can receive numerous different types of signal molecule simultaneously.

Signal molecules can be categorized into two types:

Extracellular signaling molecule (propagates message from one cell to another)
Intracellular signaling molecule (propagates message within the same cell
Extracellular signaling molecules are released by one cell and binds to target cell for message propagation. These molecules include proteins, small peptides, hormones, amino acids, fatty acid derivatives, etc.
Intracellular signaling molecules propagate message within the same cell. Various intracellular proteins act as signaling molecules and they are categorized under three classes: protein kinases, GTPase switch proteins, and adaptor proteins.¹

Types of Signaling

On the basis of the distance a signaling molecule has to travel, signaling can be of following four types:

Paracrine signaling
Endocrine signaling
Autocrine signaling
Juxtacrine signaling

Fig: Different forms of cell signaling. (Source: Introduction to molecular and cell biology, Katherine Mattaini)

Paracrine signaling

Paracrine signaling involves travel of signal molecules to short distances. Paracrine acts near the site of their release. These are released only in small amount. They get degraded before they can travel long distances.² The signaling molecules are referred to as autocoids or local hormones. Neuronal signaling is an example of paracrine signaling. It is mediated by neurotransmitters released from the synaptic vesicles when triggered by an electrical impulse.¹

Endocrine signaling

Endocrine signaling involves travel of signal molecules to long distances. Hormones are produced by an endocrine gland and send along the blood stream to distant cells. Hormones can be small lipophilic molecules that diffuse through the cell membrane to reach cytosolic or nuclear receptor or they may be water soluble molecules that bind on the plasma membrane.¹They may be proteins like insulin and glucagon, or small charged molecules like histamine and epinephrine.

Autocrine signaling

Autocrine signaling involves the response of cells to the molecules they produce themselves. Hence, it is also referred to as self-signaling. It is involved in the immune system and it frequently contributes to uncontrolled growth of cancer cells. Cancer cell produce a factor to which they respond, inducing their own unregulated proliferation. Examples of autocrine signaling include many growth factors. Prostaglandins, lipophilic hormones as a part of endocrine signaling bind to membrane receptors and are often used in paracrine and autocrine signaling. They help to modulate the effect of other hormones.²

Juxtacrine signaling

Juxtacrine signaling also known as contact-dependent signaling is mediated by ligands and receptors anchored in the cell membrane.¹The signaling molecule gets attached to the membrane of the signaling cell and a cell that comes in contact with it, receives the signal.

Types of signal receptors

There are numerous receptor classes that are used in different signaling pathways. The two of more predominant classes are as follows:

Cell surface receptors

Cell surface receptors are embedded in the plasma membrane and form the largest category of signal receptors. When an extracellular signaling ligand binds to cell surface receptor, the receptor generates an intracellular signal in response and itself undergoes conformational change. This initiates the signal transduction process, in which a signal is passed along a cell, being transformed from one form to another.

Some of the important classes of cell surface receptor are as follows:

Enzyme linked receptor

Some receptors function as enzymes while others activate enzyme. Enzyme-linked receptors are mostly either kinases or closely linked with protein kinases.

Enzyme-linked receptor have five major classes:

Receptor guanylyl cyclases
Receptor tyrosine kinases (RTKs)
Tyrosine-kinase associated receptors
Receptor tyrosine phosphatases
Receptor serine/threonine kinases(RSTKs)

G–protein coupled receptor (GPCRs)

When a ligand binds to GPCRs, it induces a conformational change in the receptor which activates a G protein. G-protein in turn activates an effector protein that generates a second messenger.

Many different mammalian cell-surface receptors contain seven membrane-spanning regions with their N-terminus on the exoplasmic face and C-terminus on the cytosolic face. GPCRs are involved in a range of signaling pathways, which includes light detection, odorant detection, and detection of certain hormones and neurotransmitters.²

Ion channel receptors

Ion channels are responsible for regulating the flows of ions across the membrane in all cells. There are specific channels for Na⁺, K⁺, Ca⁺ and Cl^– and the structure depend on the ions they conduct. Specific species of ion are conveyed through the membrane.¹ In some, ion channels, passage through the pore is governed by a ‘gate’ which may be open or closed by chemical, or electrical gradient, electrical signals, temperatures or mechanical force, depending upon the type of channel. The permeability of the channel depends on the size, extent of hydration and the charge density.

Intracellular receptors

They are located either in the cytoplasm or the nucleus. Several signaling molecules are small and lipid soluble and permitted to cross the plasma membrane to act on the intracellular receptors. Several drugs and hormones that bind to nuclear receptors show a delayed response. Many hormones cannot diffuse across the cell membranes, thus, they act on cell-surface receptors.

Reference

S.C. Rastogi. Cell and Molecular Biology. Third edition. New Age International Publishers
Lodish, Berk, Matsudaira, et al. Molecular Cell Biology. Fifth edition. W. H. Freeman; 2008.