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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
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Netrin Synergizes Signaling and Adhesion through DCC.

Rob Meijers1, Robert G Smock1, Yan Zhang2

  • 1European Molecular Biology Laboratory (EMBL), Hamburg Outstation, Notkestrasse 85, D-22607 Hamburg, Germany.

Trends in Biochemical Sciences
|November 10, 2019
PubMed
Summary

Netrin, a key axon guidance molecule, mediates conditional cell adhesion and migration. Its function is linked to signaling and coordinated by local environmental cues.

Keywords:
Axon guidanceDraxinUNC5conditional adhesionfasciculationglycosaminoglycanshaptotaxis

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Netrin is a well-established axon guidance cue.
  • Previous studies elucidated netrin's interactions with its receptors, like DCC, and co-factors.
  • Recent genetic evidence points to netrin's role in neuronal haptotaxis, involving reversible adhesion.

Purpose of the Study:

  • To propose netrin's involvement in conditional adhesion, a process critical for cell adhesion and migration.
  • To highlight the link between netrin-mediated adhesion and signaling.
  • To emphasize the role of local environmental factors in coordinating netrin function.

Main Methods:

  • Structural biology studies to understand molecular interactions.
  • Genetic studies to investigate functional roles in neuronal guidance.
  • Integration of structural and genetic data to propose a new model.

Main Results:

  • Netrin can mediate trans-adhesion between cells when the auxiliary cue draxin is present.
  • Netrin-mediated adhesion is proposed to be a reversible and localized process.
  • Netrin's adhesion and signaling functions are suggested to be interconnected.

Conclusions:

  • Netrin functions in conditional adhesion, contributing to cell adhesion and migration.
  • Netrin's activity is modulated by local tissue microenvironments.
  • The interplay between netrin, its receptors, and environmental cues is crucial for precise biological functions.