Did you know that cells such as neurons and glial cells can coordinate activities with each other? They do this by communicating through juxtacrine signaling, a process by which cells that are in direct contact with one another can communicate with each other.
- First, we will look at the definition of cell signaling and juxtacrine signaling.
- Then, we will learn the difference between juxtacrine and paracrine signaling.
- After, we will dive in the juxtacrine signaling process and look at the juxtacrine signaling diagram.
- Lastly, we will look at some examples.
Types of Cell Signaling
Cell signaling is the process wherein a cell responds to signaling molecules called ligands in its external environment through protein receptors.
There are four major types of cell signaling:
Autocrine
Paracrine
Endocrine
Juxtacrine signaling
Let’s briefly define each of these types and cite some notable examples.
Autocrine Signaling
Autocrine signaling is a type of cell signaling in which ligands bind to receptors within the same cell. A virus-infected cell, for example, can transmit autocrine signals to itself to induce apoptosis or “programmed cell death”, isolating and eliminating the virus in the process.
When target cells are nearby cells of the same type, it is typically also considered as autocrine signaling. During embryological development, for example, a group of nearby cells can be activated by autocrine signals to aid direct the differentiation of identical cells into comparable cell types.
Apoptosis is a mechanism by which cells die in a controlled manner while keeping potentially dangerous substances from escaping.
Paracrine Signaling
Paracrine signaling is the process by which cells communicate locally with nearby cells.
During paracrine signaling, ligand molecules are immediately broken down by enzymes or eliminated by nearby cells so that the response is kept localized. By breaking them down, the concentration gradient is restored, enabling signals to once again diffuse across intracellular space.
An example of paracrine signaling is the transmission of ligands called neurotransmitters between nerve cells.
Endocrine Signaling
Endocrine signaling is the process by which cells in an organism receive signals from cells in distant parts of the body. In the body, such signals come from endocrine cells, which are typically found in endocrine glands such as the thyroid gland, the pituitary gland, and the hypothalamus.
An example of endocrine signaling is the transmission of hormones like insulin, cortisol, and estrogen.
Hormones are ligands that are produced in one part of the body and travel through the bloodstream to create biological changes in other parts of the body.
What is Juxtacrine Signaling?
Finally, let's get to the main subject of our article: juxtacrine signalling.
Juxtacrine signaling (also known as direct cell signaling) is the process by which cells that are in direct contact with one another communicate with each other.
When neighboring cells are physically in contact with each other, juxtacrine signaling occurs. A cell's membrane binds the signaling molecule in this case, so it is not free to travel. Then, it may interact with a receptor on an adjacent cell's membrane.
Juxtacrine Signaling vs Paracrine Signaling
Given that juxtacrine signaling is defined as a type of signaling that occurs between adjacent cells whereas paracrine signaling occurs between nearby cells, it is easy to confuse the two.
To put it simply, what makes the two different is that juxtacrine signaling requires the cells to be physically touching, whereas paracrine signaling does not require any contact; instead, it relies on the diffusion of signaling molecules from cell to cell.
Diffusion is the passive movement of substances from an area of higher to lower concentration.
| Table 1. Differences between paracrine and juxtacrine signaling |
|---|
| Paracrine Signaling | Juxtracrine Signaling |
| Definition | Signal released by a cell to act on neighboring cells | Signal transmitted through direct contact between cells |
| Signaling molecule | Diffusible molecules (e.g., cytokines) | Membrane-bound ligands, gap-junctions |
| Target cells | Nearby cells within a tissue | Adjacent cells that are in direct contact |
| Distance | Short range (micrometers to millimeters) | Very short range (cell-cell contact) |
| Examples | Growth factor signaling | Notch signaling in development |
Juxtacrine Signaling vs Autocrine Signaling
The main difference between juxtacrine and autocrine signaling is that autocrine signaling involves only one cell (the messenger cell is also the receptor cell), while juxtacrine signaling involves at least two cells that are beside each other. There are other differences too:
| Table 2. Differences between autocrine and juxtacrine signaling |
|---|
| Autocrine Signaling | Juxtracrine Signaling |
| Definition | Signaling cells secrete signaling molecules that bind to receptorson their own cell surface | Signaling cells secrete signaling molecules that bind to receptors on an adjacent cell surface |
| Signaling molecule | The signaling molecule is usually a cytokine or growth factor | The signaling molecule is usually a membrane-bound protein or a diffusable molecule (gap junctions) |
| Function | Allows cells to regulate their own behavior and maintain homeostasis | Used for cell-to-cell communication during development and differentiation |
| Function examples | Can be involved in the progression of cancer and other diseases | Involved in immune responses and tissue repair, and signal coordination |
| Signaling molecule examples | Examples include interleukin-2, transforming growth factor-beta, and tumor necrosis factor-alpha | Examples include Notch signaling, Delta-Notch signaling, and Jagged-Notch signaling |
Juxtacrine Signaling Pathway
Because juxtacrine signaling requires physical contact, the mechanisms and dynamics underpinning juxtacrine signaling are quite different from other types of signaling. Signal exchange takes place locally at the interface between the two adjacent cells.
Such an exchange can be bidirectional (meaning the signal moves in both directions) and asymmetric. This is shown in the diagram below (Fig. 1)
An example of a juxtacrine signaling pathway is the Notch pathway. The Notch pathway is a juxtacrine signaling pathway in which the cells sending the signal have membrane-bound ligands (specifically transmembrane proteins from the Delta/Serrate/Lag-2 [DSL] family) which bind to and activate cell-surface Notch receptors on the receiving cell (Fig. 3).
When the Notch receptor is activated, the Notch intracellular domain (NICD) is cleaved and translocated to the nucleus where it binds to a certain transcription factor, thereby inducing the transcription of target genes.
Signals exchanged between adjacent cells through the Notch signaling pathway amplify cell differentiation, determine the fate of a cell, and enable pattern formation during development. Cell differentiation is the formation of different cell types such that when these cells are organized into tissues, they are imbued with a specific physiological function.
The activation of Notch signaling in intestinal epithelial cells (cells lining the intestine) increases cell differentiation in favor of absorptive enterocytes; whereas its inhibition tips the scale towards hormone-secreting enteroendocrine cells, mucus-secreting goblet cells, and enzyme-secreting Paneth cells–all of which are of secretory lineage.
Notch signaling also plays a role in the nervous system. For example, in the vertebrate nervous system, the binding of Delta proteins to Notch receptors indicate the receiving cell not to become neural, whereas, in the vertebrate eye, the binding of ligands to Notch receptors regulates which cells become glial cells and which become optic neurons.
Juxtacrine Signaling Diagram
As the cell surface interacts with juxtacrine ligands and receptors, the protein and lipid components of the signaling surfaces undergo radical remodeling. Signaling complexes in the juxtaposed cells are spatially and physically connected via ligand-receptor engagement and surface reconfiguration.
Cell-to-cell communication through juxtacrine signaling plays an important role in many different developmental, physiological, immunological, neurological, and pathological processes.
Types of Juxtacrine Signaling
Juxtacrine signaling can happen in many different ways but some of the most common are gap junctions and plasmodesmata. Gap junctions and plasmodesmata are used to facilitate juxtacrine signaling.
In this section, we will discuss what gap junctions and plasmodesmata are and how they facilitate juxtacrine signaling. We will also discuss an example of a juxtacrine signaling pathway called Notch pathway.
Juxtacrine Signaling through Gap Junctions
Gap junctions are regions in the cell membrane that function as communication channels between adjacent cells. Cells linked via gap junctions are called “coupled” cells. Small soluble signaling molecules including ions are able to travel through these junctions.
Connexin proteins make up gap junction channels. Six identical connexins in the membrane of each cell combine together to form a transmembrane channel with a central pore. One cell's channel complex connects to another cell's channel complex, allowing the cytoplasms of both cells to be linked.
An example of a pathway that uses gap junctions is calcium (Ca2+) signaling, which involves the diffusion of various molecules including ATP through the extracellular space, thereby activating P2 receptors (Fig. 2).
This intracellular propagation of Ca2+ waves from one cell to an adjacent cell requires gap junctions which enable the movement of signaling molecules across coupled cells. The intracellular propagation of Ca2+ waves is thought to be one of the ways by which cell activity is coordinated, for instance between neurons and glial cells in the central nervous system.
Juxtacrine Signaling through Plasmodesmata
Plasmodesmata are plant cellular structures that facilitate direct cell-to-cell communication between neighboring cells. These serve as the bridges between the cytoplasm of two cells that are separated by cell walls.
The structure of plasmodesmata varies greatly during a cell’s growth and differentiation, or between different cell-cell junctions, depending on the intercellular transport requirements.
A typical plasmodesma (this is the singular form of plasmodesmata) has a pore size of 20-50 nm and consists of a single membrane-lined cytoplasmic channel bridging two cells, but it can be modified such that it becomes branched or complex, with many channels that merge, split, or share the same opening. Simple and complex plasmodesmata control intercellular signaling differently, with complex plasmodesmata acting like a filter, narrowing the range of chemicals that can move between cells.
An example of signaling that occurs through plasmodesmata is the defense signal propagation: when exposed to pathogens, the lipid transfer protein azelaic acid induced 1 (AZI1) triggers systemic acquired resistance (SAR), leading to the transport of SAR signaling molecules through the plasmodesmata. The propagation of such defense signals help plants prepare distant parts for impending threats or external biotic or abiotic stresses.
Examples of Juxtacrine Signaling
Juxtacrine signaling is used across the whole body of animals, and also in plants. It allows for very fast communication and coordination, so it is crucial for processes where speed is essential. Here are some examples of juxtacrine signaling:
- Myocardiocytes (heart muscle cells) are connected through gap junctions. This allows chemical and electrical signals to travel really fast across multiple cells. Speed is essential here because myocardiocytes need to depolarise and contract all in synchrony so that the heart can pump blood through an organism effectively.
- The same thing happens between the neurons of certain regions of the nervous system. The lungs need to contract and expand in synchrony so that an organism can breathe well. Therefore, the neurons that regulate this process require gap junctions to communicate with speed and be able to coordinatedly signal to the muscles that regulate breathing.
Juxtacrine Signaling - Key takeaways
- Juxtacrine signaling (also known as direct signaling) is the process by which cells that are in direct contact with one another communicate with each other.
- When neighboring cells are physically in contact with each other, juxtacrine signaling occurs. A cell's membrane binds the signaling molecule in this case, so it is not free to travel. Then, it may interact with a receptor on an adjacent cell's membrane.
- Juxtacrine signal exchange takes place locally at the interface between the two adjacent cells. Such an exchange can be bidirectional and asymmetric.
- Gap junctions in animal cells and plasmodesmata in plant cells are frequently used to facilitate juxtacrine signaling.
- An example of a juxtacrine signaling pathway is the Notch pathway. Signals exchanged between adjacent cells through the Notch signaling pathway amplify cell differentiation, determine the fate of a cell, and enable pattern formation during development.
References
- Momiji, Hiroshi, et al. “Disentangling Juxtacrine from Paracrine Signalling in Dynamic Tissue.” Disentangling Juxtacrine from Paracrine Signalling in Dynamic Tissue | PLOS Computational Biology, journals.plos.org, 13 June 2019, https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007030.
- Ross E. Sager, Jung-Youn Lee; Plasmodesmata at a glance. J Cell Sci 1 June 2018; 131 (11): jcs209346. doi: https://doi.org/10.1242/jcs.209346
- Kume, Tsutomu. (2009). Novel insights into the differential functions of Notch ligands in vascular formation. Journal of angiogenesis research. 1. 8. 10.1186/2040-2384-1-8.
- Mammano F. Gap Junctions: Cell-Cell Channels in Animals. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6455/
- “Cell - Cell Differentiation.” Encyclopedia Britannica, www.britannica.com, https://www.britannica.com/science/cell-biology/Cell-differentiation. Accessed 30 July 2022.
- “Intro to Chemical Signaling and Communication by Microbes | Organismal Biology.” Intro to Chemical Signaling and Communication by Microbes | Organismal Biology, organismalbio.biosci.gatech.edu, https://organismalbio.biosci.gatech.edu/chemical-and-electrical-signals/intro-to-chemical-signaling-and-signal-transduction/. Accessed 30 July 2022.
- “Research | The Jun Group.” Research | The Jun Group, junlab.ucsf.edu, https://junlab.ucsf.edu/article/research. Accessed 30 July 2022.
- Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Juxtacrine Signaling. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10072/
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