membraneanchored

Membrane-anchored refers to molecules that remain associated with cellular membranes, most commonly proteins, but also lipids and other macromolecules. Anchoring can be covalent, as in lipid-anchored proteins, or via integral transmembrane domains, or through strong noncovalent interactions that tether a molecule to the membrane. Membrane-anchored proteins are localized to the plasma membrane or to the membranes of intracellular organelles and play diverse roles in signaling, adhesion, transport, and enzymatic activity at the cell surface.

Anchor types include transmembrane proteins that span the lipid bilayer with one or more hydrophobic segments; GPI-anchored proteins tethered to the outer leaflet by a glycosylphosphatidylinositol anchor; lipid-anchored proteins carrying covalently attached fatty acids or prenyl/sterol groups, enabling peripheral association with membrane leaflets; and peripheral membrane proteins that bind to membrane lipids or to other membrane-anchored components. Some proteins can switch between anchored and soluble forms via proteolytic cleavage or release of the anchor.

Anchored proteins are synthesized in the secretory pathway. Transmembrane proteins are integrated into the ER membrane and delivered to membranes as part of trafficking. GPI-anchored proteins receive a GPI moiety in the endoplasmic reticulum, which anchors the protein to the outer leaflet. Lipidation occurs during or after translation, attaching fatty acids or isoprenoid groups to specific amino acids.

At the cell surface, membrane-anchored proteins participate in signal transduction, cell adhesion, recognition, and enzymatic processes. They can be regulated by shedding or proteolytic release, generating soluble forms that act at a distance. Lipid-anchored and GPI-anchored proteins often reside in membrane microdomains that facilitate interactions.

Examples include GPI-anchored surface proteins such as PrP and CD59, transmembrane receptors and adhesion molecules, and membrane-anchored enzymes. Mislocalization or altered anchoring can contribute to disease states by disrupting signaling pathways or cell–cell interactions.