Juxtacrine Signaling

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.

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.

What is Juxtacrine Signaling?

Finally, let's get to the main subject of our article: juxtacrine signalling.

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.

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:

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.

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.

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.

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.