S377 Chapter 16

Cell adhesion is a property of many cell types which position themselves by attaching to other cells or to the ❌ matrix using adhesion molecules in the ❌

Some adhesion molecules also ❌ signals from the ❌ environment to the cell

Cell migration involves both the interaction of adhesion molecules with elements of the ❌, and the coordinated attachment, ❌ and detachment of adhesion molecules from the extracellular matrix.

The slime mould Dictyostelium discoideum and mammalian ❌ are the best-studied examples of mobile eukaryotic cells. The basic processes of motility are similar in all ❌.

❌ is the overall strength of cellular ❌, which is determined by the ❌ of adhesion molecules in a localized region of the plasma membrane, and by the affinity of ❌ adhesion molecules.

❌ mediate cell–cell junctional adhesion via ❌ interactions, and are associated with the ❌ via anchoring proteins called ❌.

❌ bind to other ❌, not other integrins. This is ❌ binding.

Loss of ❌ function in tumours is associated with ❌, as it means a loss of ❌ cell adhesion.

Cadherins bind to ❌. Integrins bind to ❌. Lectins bind to ❌. ❌ are a type of lectin.

Integrins are very important in controlling cell ❌, as their affinity may be modulated by ❌ signalling.
The ❌ dependent adhesion site on the ❌ of integrins can be present in an open or closed form, which determines whether the integrin can bind to its substrate(s).

Different integrins can bind to components of the ❌ or adhesion molecules on ❌. Some integrins also transduce ❌ for anchorage-dependent cells.

❌ CAMs contain several ❌ domains. By contrast with i❌ and c❌, binding of Ig superfamily CAMs to their ligands is independent of ❌.

C❌, ❌ and l❌ are important components of the ECM and ❌, and bind to different ❌.

I❌, Ig superfamily cell adhesion molecules (Ig superfamily CAMs) and s❌ are all involved in ❌ into tissues, each type of molecule having a different function in the process. Selectins bind to
❌ to tether migrating cells, whereas the interaction between integrins on the ❌ and Ig superfamily CAMs on the ❌ allows the leukocyte to migrate through the ❌.

Cells can regulate the functional activity of their adhesion molecules by changing the surface ❌ or distribution of the molecules (❌), and/or by modulating their ❌. e.g. the ❌ modulation of ❌ affinity

Adhesion molecules tend to cluster in high-❌ patches (which are called ‘❌’ in cell–matrix interactions).

Adhesion can be rapidly modulated by changing the ❌ of the individual adhesion molecules.
Alternatively, adhesion can be downregulated by ❌ or shedding adhesion molecules from the ❌.

At the leading edge of the ❌, ❌ filaments form ❌.
❌ attach to the side of filaments and add new ones, forming branches.
❌ inhibits this by ❌. ❌ promotes it by adding actin to the forming branches. The balance between them determines ❌.
Actin monomers are added to the plus end, as T-form (i.e. ❌), over time it hydrolyses to D-form (i.e. ❌). ❌ binds to ❌ and helps to degrade the ❌ where most of the D-form is.
Some ❌ are capped, which stops further growth. Most plus ends in ❌ are capped.

Many ❌, including integrins and Ig superfamily CAMs interact with ❌ via ❌. Engagement of adhesion molecules with the ❌ depends on the arrangement of the cell and whether the cell has been activated by ❌.

The ❌ proteins –e❌, r❌ and m❌ –act as cytoskeletal anchoring proteins for several transmembrane proteins including ❌. Following activation, these proteins switch to an ❌, which cross-links the adhesion molecule to ❌.

α -Actinin, ❌ and talin are involved in cross-linking ❌ to ❌.

❌ interacts with filaments, to maintain the ❌ of the cell, for moving the cell ❌ and to move ❌.

❌ molecules promote ❌ of cells and ❌ migration. In multicellular animals, many chemotactic molecules act on ❌ transmembrane ❌ receptors.

❌ are a large group of chemotactic molecules which control ❌ migration. They have a ❌ binding site (GAGs may be located in the extracellular matrix or on the surface of cells),
and a ❌ binding site.

Binding of ❌ molecules to their receptors can lead to the activation of ❌ and the ❌ of membrane lipids, which recruit proteins with ❌ (PH) domains to the leading edge of the cell and modulate interactions between the ❌ and adhesion molecules.

Chemokines and their receptors are not very ❌. Many of the receptors will bind several types of ligand and many chemokines will bind to several different receptors. This is called ❌.

Activation of GTPases belonging to the ❌ has global effects on cell morphology, the arrangement of the ❌, and cell adhesion properties. Prenylation of RhoA translocates it to the plasma membrane, where it can be activated by GTP binding and modulate the F-actin network by formation of focal adhesions.

Molecular interactions between the ❌ induced by different ❌ allow cells to regulate their overall patterns of ❌ within the complex gradients of chemotactic (or repellent) molecules that may be found in vivo .

❌ proteins expressed on the cell surface are ❌ proteins that act on ❌ and can prevent ❌ into tissues expressing the Slit proteins. Slits and Robos are widely and transiently expressed during ❌, and are still present in the adult in many tissues.

❌ (MMPs) are secreted by ❌, which allows them to move through tissues by ❌ of the extracellular matrix.

❌ (ADAMs) interfere with ❌, and also can facilitate leukocyte ❌.

MMPs and ADAMs are ❌ by tissue inhibitors of metalloproteases (❌). The balance of the enzymes and inhibitors is important in controlling cell ❌ and tissue ❌.