Cell Signaling

Cell Signaling Definition

Cell signaling refers to the vast networks of communication that occur between and within each cell in our body. Unlike the stable bricks that lay the foundation of our houses, cells are dynamic and ever-active building blocks. Cell signaling makes this possible. Together, cells are able to coordinate everything from neonatal development to large, cascading immune responses against bacteria or viruses.

Three Stages of Cell Signaling

At its core, however, cell-to-cell signaling can simply be described as the production of a “signal” by one cell that is then received by its “target” cell. In effect, signal transduction is said to have three stages:

  1. Reception, whereby the signal molecule binds the receptor
  2. Transduction, which is where the chemical signal results in a series of enzyme activations
  3. Finally, the response, which is the resulting cellular responses.

Cell Signaling Pathways

Typically, cell signaling is either mechanical or biochemical and can occur locally (autocrine, paracrine), or from a distance (endocrine). The labeling itself is contingent on the distance between the original cell and target cell, and on the physical properties of the signal (“ligand”). Hydrophobic ligands have fatty properties and include steroid hormones and vitamin D3, etc. Following the like-dissolves-like concept, these molecules are able to diffuse across the target cell’s plasma membrane to bind intracellular receptors inside. On the other hand, hydrophilic ligands are often amino-acid derived and will bind to receptors on the surface of the cell; being aqueous allows the signal to travel through the aqueous environment of our bodies without assistance.

Protein molecular structure
The image depicts a cartoon representation of the molecular structure of a protein receptor binding to a ligand.

Types of Signaling Molecules

Signaling molecules are currently assigned one of five classifications.

  • Intracrine ligands are produced by the target cell itself and bind to a receptor within.
  • Autocrine ligands are finely distinct in that although they are also made by the target cell, they are first secreted and then later bind to the cell as well as neighboring cells (ex. Immune cells).
  • Juxtacrine ligands target adjacent cells (often called “contact-dependent” signaling).
  • Paracrine ligands target cells in the vicinity of the original emitting cell (ex. Neurotransmitters like Acetylcholine).
  • Lastly, Endocrine cells produce hormones that have the important task of targeting distant cells and often travel through our circulatory system.

Cell Signaling Function and Key Players

As mentioned previously, cell signaling serves a vital purpose in allowing our cells to carry out life as we know it. Thanks to the concerted efforts of our cells via their signaling molecules, our body is able to orchestrate the many complexities that maintain life. These complexities, in effect, demand a diverse collection of receptor-mediated pathways that execute their unique functions.

Intracellular Receptors

A common type of signaling receptor are Intracellular Receptors, which are located within the cytoplasm of the cell and generally include two types. Nuclear receptors are a class of protein with diverse DNA binding domain that, when bound to steroid or thyroid hormones, form a complex that enters the nucleus and modulates the transcription of a gene. IP3 receptors are another class, which are located in the endoplasmic reticulum and carry out important functions like the release of Ca2+ that is so crucial for the contraction of our muscles and plasticity of our neural cells.

Ligand-gated ion channels

Spanning our plasma membranes are another type of receptor called Ligand-gated ion channels that allow hydrophilic ions to cross the thick fatty membranes of our cells and organelles. When bound to a neurotransmitter like acetylcholine, ions (commonly K+, Na+, Ca2+, or Cl) are allowed to flow through the membrane to allow the life-sustaining function of neural firing to take place, among many other functions!

G protein coupled receptors

Moving on to a diverse family of cell surface receptors, G protein coupled receptors (GPCRs) remain the largest and most diverse group of membrane receptors in eukaryotes. They are special in that they receive input from a diverse group of signals ranging from light energy to peptides and sugars. Their mechanism of action also starts with a ligand binding to its receptor. However, the demarcation is that ligand binding results in the activation of a G protein that is then able to transmit an entire cascade of enzyme and second messenger activations that carry out an incredible array of functions like sight, sensation, inflammation and growth.

Receptor Tyrosine Kinases

Receptor Tyrosine Kinases (RTKs) are another class of receptors revealed to show unforeseen diversity in their actions and mechanisms of activation. The general method of activation follows a ligand binding to the receptor tyrosine kinase, which allows their kinase domains to dimerize. This dimerization then invites the phosphorylation of their tyrosine kinase domains that, in turn, allow intracellular proteins to bind the phosphorylated sites and become “active.” An important function of receptor tyrosine kinases are their roles in mediating growth pathways (i.e., Epidermal Growth Factors, Fibroblast Growth Factors). Of course, the downside of having complex signaling networks lies in the unforeseen ways in which any alteration can produce disease or unregulated growth – cancer. Much is yet to be understood about cell signaling pathways, but one appreciable fact is that the importance they carry is nothing short of monumental.

Signal transduction
This figure depicts various forms of RTK and GPCR-mediated Signal Transduction.

Quiz

1. Correctly name the types of signaling molecules mentioned in the article:
A. Paracrine, Cytocrine, Autocrine, Endocrine, Pathocrine
B. Cytocrine, Autocrine, Paracrine, Intracrine, Juxtacrine
C. Intracrine, Paracrine, Autocrine, Endocrine, Juxtacrine
D. Exocrine, Autocrine, Paracrine, Juxtacrine, Intracrine

Answer to Question #1

2. Define Endocrine signaling:
A. Passage of signal between neighboring cells
B. Signal travels distance to target cell
C. Emitting cell is also recipient cell

Answer to Question #2

3. Name the distinction between Juxtacrine and Paracrine signals:
A. Juxtacrine signals are contact-dependent and affect adjacent cells whereas paracrine signals target cells in the vicinity
B. Paracrine signals are contact-dependent and affect adjacent cells whereas juxtacrine signals target cells in the vicinity
C. Juxtacrine signals travel through the bloodstream to get to target cell, whereas Paracrine signals remain local

Answer to Question #3

References

  • Cooper GM. (2000). The Cell: A Molecular Approach. 2nd edition. Signaling Molecules and Their Receptors. Sunderland (MA): Sinauer Associates. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9924/
  • Boundless.com (2017). Forms of Signaling. Concept Version 6. Date accessed April 29, 2017; available from: https://www.boundless.com/biology/textbooks/boundless-biology-textbook/cell-communication-9/signaling-molecules-and-cellular-receptors-83/forms-of-signaling-380-11606/
  • Ritter, S.L. & Hall, R.A. (2009). Fine-tuning of GPCR activity receptor-interacting proteins. Nature Reviews Molecular Cell Biology 10, 819-830. Doi:10.1038/nrm2803
  • Khan Academy (2017). How Cells Signal to Each Other: Ligands and Receptors. Date accessed April 28, 2017; available from: https://www.khanacademy.org/science/biology/cell-signaling/mechanisms-of-cell-signaling/a/signal-perception
  • Lemmon, M. and Schlessinger, J (2010). Cell. Volume 141, Issue 7; 1117-1134. Cell Signaling by Receptor Tyrosine Kinase. Available from: http://www.cell.com/cell/fulltext/S0092-8674(10)00665-3?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867410006653%3Fshowall%3Dtrue
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