Plasma membrane-located receptor

Figure 10.7 The EGF receptor. The N-terminal, extracellular region of the receptor contains 622 amino acids. It displays two cysteine-rich regions, between which the ligand-binding domain is located. A 23 amino acid hydrophobic domain spans the plasma membrane. The receptor cytoplasmic region contains some 542 amino acids. It displays a tyrosine kinase domain, which includes several tyrosine autophosphorylation sites, and an actin-binding domain that may facilitate interaction with the cell cytoskeleton...

Molecular communication is the characteristic information system in the bioinformation networks. The endocrine system, which is one of intermolecular information networks, may represent the feature of molecular communication. The gland is a collection of specialized cells that synthesize, store, and release hormones. A hormone, molecular information, is released into the extracellular fluid and transported via the blood to two types of cells target cells where the hormone acts, and other cells that degrade the hormone as schematically presented in Fig.l. In some systems the target cell and the degradation site are in the same organ or even the same cell. Both activities may even be located on the same plasma membrane. The receptor for the hormone is located on the surface of the plasma membrane. 

Receptors are proteins or glycoproteins found either on the surface of the target cell or located within the cell interior. The surface receptors engage peptide hormones which, being hydrophilic, do not traverse the fatty plasma membrane intracellular receptors combine specifically with particular steroids or tri-iodothyronine, T3. 

Biochemically, most quaternary ammonium compounds function as receptor-specific mediators. Because of their hydrophilic nature, small molecule quaternaries caimot penetrate the alkyl region of bdayer membranes and must activate receptors located at the cell surface. Quaternary ammonium compounds also function biochemically as messengers, which are generated at the inner surface of a plasma membrane or in a cytoplasm in response to a signal. They may also be transferred through the membrane by an active transport system. 

The biological actions of adrenaline and noradrenaline are mediated via nine different G-protein-coupled receptors, which are located in the plasma membrane of neuronal and nonneuronal target cells. These recqrtors are divided into two different groups, a-adrenergic receptors and P-adrenergic recqrtors (see P-adrenergic system). 

GPCR function has been shown to be regulated by several different mechanisms. The number of receptors on the plasma membrane may be regulated by transcription, mRNA stability, biosynthetic processing, and protein stability. In addition, the function of receptors in the plasma membrane can be influenced by regulatory phosphorylation and by association with other proteins that determine the subcellular location of receptors relative to other signaling molecules. 

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

Because of their strategic localization, astrocytes play a crucial role in maintaining the extracellular ionic homeostasis, provide energetic metabolites to neurons and remove excess of neurotransmitter in schedule with synaptic activity. In addition, the strategic location of astrocytes allows them to carefully monitor and control the level of synaptic activity. Indeed, number of papers during the last 15 years have shown that cultured astrocytes can respond to a variety of neurotransmitters with a variety of different patterns of intracellular calcium increases (Verkhratsky et al. 1998). Later on, studies performed in intact tissue preparations (acute brain slices) further established that the plasma membrane receptors can sense external inputs (such as the spillover of neurotransmitters during intense synaptic activity) and transduce them as intracellular calcium elevations, mostly via release of calcium from internal stores (Dani et al. 1992 Murphy et al. 1993 Porter and McCarthy... 

G -protein-coupled receptors are often located on the presynaptic plasma membrane where they inhibit neurotransmitter release by reducing the opening of Ca2+ channels like inactivation and breakdown of the neurotransmitter by enzymes, this contributes to the neuron s ability to produce a sharply timed signal. An a2 receptor located on the presynaptic membrane of a noradrenaline-containing neuron is called an autoreceptor but, if located on any other type of presynaptic neuronal membrane (e.g., a 5-HT neuron), then it is referred to as a heteroreceptor (Langer, 1997). Autoreceptors are also located on the soma (cell body) and dendrites of the neuron for example, somatodendritic 5-HTia receptors reduce the electrical activity of 5-HT neurons. 

Figure 5.10 Ribbon diagram of the transferrin receptor dimer depicted in its likely orientation with regard to the plasma membrane. One monomer is blue, the other is coloured according to domain the protease-like, apical and helical domains are red, green and yellow respectively the stalk is shown in grey, connected to the putative membrane spanning helices in black. Pink spheres indicate the location of Sm3+ ions. Reprinted with permission from Lawrence et ah, 1999. Copyright (1999) American Association for the Advancement of Science.

NMDA and AMPA receptors are spread across the post-synaptic density (PSD), whereas metabotropic glutamate receptors (except mGluR7) are located along the periphery of the PSD (Fig. 15-2). NMDA receptors appear to be present at most or all glutamatergic synapses whereas the content of AMPA receptors is variable - from zero to about 50 receptors per PSD [33]. Some synapses are silent , meaning that activation of them does not elicit AMPA receptor currents when the plasma membrane is hyperpolarized and Mg2+ blocks NMDA receptors. Such silent synapses contain only NMDA receptors. However, AMPA receptors are recruited from the cytosol to the PSD to activate such silent synapses in LTP. 

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