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Most Receptors Are on the Cell Surface

Water-soluble signalling molecules cannot cross the membrane lipid bilayer, but bind to specific receptors embedded in the plasma membrane. The receptors have an extracellular domain that binds the signalling molecule, a hydrophobic transmembrane domain and an intracellular domain.

Binding of a ligand induces a conformational change in the receptor, in particular that of its intracellular region. It is this conformational change that activates a relay of intracellular signalling molecules, ultimately bringing about the appropriate cellular response represented in Figure 2.

Receptors can be classified structurally into single-pass transmembrane receptors (with one extracellular, one transmembrane and one intracellular region) and multipass transmembrane receptors.However, in terms of their signal transduction characteristics, it is easier to distinguish four groups of receptors (Figure 4).

Figure 4 The four major classes of membrane receptors: (a) ion-channel receptors; (b) 7-helix transmembrane receptors (7TM receptors); (c) receptors with intrinsic enzymatic activity (RIEA); (d) enzyme-associated receptors (recruiter receptors).

  1. Receptors that also serve as the effector For example, one type of acetylcholine receptor is also an ion channel, and belongs to a family of receptors called ion-channel receptors. In response to acetylcholine, these receptors allow the passage of specific ions, thereby effecting changes in the membrane potential of a cell. Acetylcholine receptors are extremely important in the transmission of electrical signals between excitable cells.
  2. 7-helix transmembrane receptors 7TM receptors possess seven membrane-spanning regions, an N-terminal extracellular region and a C-terminal intracellular tail. The mechanism of activation of most 7TM receptors involves coupling to G proteins, and in this case they are also called G protein-coupled receptors (GPCRs). Adrenalin receptors are examples of GPCRs.
  3. Receptors whose intracellular tail contains an enzymatic domain, which are known as receptors with intrinsic enzymatic activity (RIEA) This group includes the receptor tyrosine kinases, involved in the response to many growth factors.
  4. Receptors that require association with cytosolic or membrane-bound proteins with enzymatic activity for signalling These receptors do not have intrinsic enzymatic activity, and have been referred to as enzyme-associated receptors or recruiter receptors (although, strictly speaking, both GPCRs and receptors with intrinsic enzymatic activity also function by recruiting cytosolic signalling molecules, as you will see in Section 3.3).
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