Juxtacrine signalling

In biology, juxtracrine signalling (or contact-dependent signalling) is a type of cell–cell or cell–extracellular matrix signalling in multicellular organisms that requires close contact. In this type of signalling, a ligand on one surface binds to a receptor on another adjacent surface. Hence, this stands in contrast to releasing a signaling molecule by diffusion into extracellular space, the use of long-range conduits like membrane nanotubes and cytonemes (akin to 'bridges') or the use of extracellular vesicles like exosomes or microvesicles (akin to 'boats'). There are three types of juxtracrine signaling:

Additionally, in unicellular organisms such as bacteria, juxtracrine signaling refers to interactions by membrane contact.

Juxtracrine signaling has been observed for some growth factors, cytokine and chemokine cellular signals, playing an important role in the immune response. Juxtracrine signaling is also involved in cell specification, or determination of a cell fate determination through a process called induction. In this process, the inducing cells send a signal to responder cells that receive the signal to activate the process of responder's cell fate determination. This cell-to-cell communication plays a role in many developmental processes, such as patterning of the embryos, establishing of cell type diversity, organogenesis, and formation of tissues in various organisms. It has a critical role in development, particularly of cardiac and neural function.

Other types of cell signaling include paracrine signalling and autocrine signalling. Paracrine signaling occurs over short distances, while autocrine signaling involves a cell responding to its own paracrine factors.

The term "juxtracrine" was originally introduced by Anklesaria et al. (1990) to describe a possible way of signal transduction between TGF alpha and EGFR.

In this type of signaling, specific membrane-bound ligands bind to a cell's membrane. A cell with the appropriate cell surface receptor or cell adhesion molecule can bind to it. Cell-cell signaling can be extrinsic and intrinsic to the cells. Intrinsic signaling indicates that cells connect more directly with the help of cadherins, ephrins, and Notch-Delta signaling pathway, thus, more intrinsically with the cell defined machinery. Juxtracrine signaling is considered an intrinsic cell-to-cell signaling as cells communicate through surface level proteins. External cell-cell signaling involves bringing out information in or out of the cell without any direct contact with cell structures, except the binding sites for the signaling molecules. Such cell-cell signaling is utilized by the paracrine and autocrine signaling.

Some of the cell signaling pathways that are involved in cell-to-cell communication include: Notch-Delta, FGF, Wnt, EGF, TGF-beta, Hedgehog, Hippo, Jun kinase, Nf-kB, and retinoic acid receptor. Of all these pathways, juxtracrine signaling utilizes Notch and Hippo the most as they involve a more direct cell-to-cell contact signaling.

Notch signaling pathway, notably involved in neural development. In the Notch signaling pathway for vertebrates and Drosophila, the receiving cell is told not to become neural through the binding of Delta and Notch. Within the eye of vertebrates, which cells become optic neurons and which become glial cells is regulated by Notch and its ligands.