Substrate adhesion molecules

An image illustrating the two main SAMs: Integrin and CD44. Extracellular domains are red in hue, transmembrane domains are blue, and intracellular domains are green. Other molecules that coordinate with the SAMs are depicted, including ECM elements like fibrin and collagen, effector molecules, and actin. The alpha and beta subunits of integrin bind to the ECM elements, while the beta subunit is bound to actin on the intracellular side via talin and vinculin. CD44 is hook-shaped, binding colorful effector molecules. One aids CD44 in binding to actin.

The substrate adhesion molecules integrin and CD44. Both are bound to extracellular matrix elements like fibronectin or collagen. Integrins have an α- and a β- subunit, the latter of which binds to actin with the aid of talin and vinculin. CD44 binds effector molecules to trigger cell signaling cascades. Extracellular, transmembrane, and intracellular domains are red, blue, and green, respectively.

Substrate adhesion molecules (SAMs), also known as cell-substrate adhesion molecules, cell-substratum adhesion molecules, substratum adhesion molecules, or cell-matrix molecules, are single-pass membrane proteins characterized by their role in binding cells to the extracellular matrix (ECM).

As it is commonly understood that individual members of this family bind ECM elements, publications often forego the SAM classification and will instead refer to these proteins under the broader classification for proteins involved in adhesion, cell adhesion molecules.

Examples

• Integrins
• CD44

Structure

The intracellular side will be anchored to the cytoskeleton (actin, in the case of integrins), while the substrate side will anchor to the ECM.

Integrins have two subunits, an α and a β. Both bind to the ECM on the substrate side, which activates the actin-binding activity of the β unit on the intracellular side. This forms what is called a focal adhesion, which enables external activity in the extracellular matrix to affect the shape and movement of the cell.

CD44 only has one subunit, with a long substrate-side N-terminal head and a short intracellular tail. The extracellular domain can bind many different molecules, including those composing the ECM. The intracellular domain can then bind with various effector proteins, including actin. CD44 is primarily involved in signaling.

Relevance in Biology

Neuronal Morphogenesis

SAMs play a key role in neuronal morphogenesis. Integrin organizes actin to aid in synaptic stability, synaptic plasticity, and dendritic stability on the dendritic end of a neuron. On the axonal end, focal adhesions are formed to aid the axon terminal in locomotion towards the proper location.

Cancer Markers

CD44 is a prominent cancer marker because it plays many important roles in cancer pathology. It can trigger the digestion of the ECM to allow metastasis, trigger angiogenesis, inhibit the P53 apoptosis monitoring system, and, when bound to hyaluronic acid, trigger the MAPK cascade to promote proliferation.

See also

• Cell adhesion molecules
• Integrin
• CD44
• Extracellular Matrix
• Fibronectin
• Laminin
• Focal Adhesion

Further reading

• Ulrich, Klaus (1994). "Cell-Adhesion Molecules of Vertebrates". Comparative animal biochemistry. Springer. ISBN 978-3-540-57420-0. Search this book on
• Haschek, Wanda M.; et al. (2009). Fundamentals of Toxicologic Pathology (2nd ed.). Academic Press. p. 635. ISBN 978-0-12-370469-6. Search this book on

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