Plasma membrane receptors

In contrast to the enhanced receptor expression that occurs during activation and priming, the expression of some receptors actually decreases during this process. This is particularly evident with receptors such as CD16 (the low-affinity receptor for IgG) and the ligand that binds monoclonal antibody 31D8 (a surface molecule of undefined nature whose expression is closely linked to fMet-Leu-Phe responsiveness). These molecules are GPI-linked and are shed from the cell surface during activation (see Fig. 3.10). 

Neutrophil priming Regulation during inflammatory activation 

their continued expression on the plasma membrane requires translocation from preformed pools and/or de novo biosynthesis. 

The fact that receptors need to be replaced via de novo biosynthesis can be demonstrated in experiments where neutrophils are cultured in the presence and absence of cycloheximide. When protein biosynthesis is blocked by this inhibitor, the expression of FcyRIII on the cell surface cannot be maintained as the cells age in culture (Fig. 7.8), indicating that continued expression of this receptor is a balance between the amount shed and the amount replaced via new biosynthesis. Newly synthesised receptors appear to be functional, because they can be detected within the biosynthetic machinery of the cell, and newly made (i.e. newly labelled) receptors are detected in the plasma membrane. 

The regulation of expression of receptors on the plasma membrane is thus controlled by several factors  

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III. Tyr protein kinases A. Cytosolic tyrosine kinases src, fgr, abl, etc.) B. Receptor tyrosine kinases (RTKs) Plasma membrane receptors for hormones such as epidermal growth factor (EGF) or platelet-derived growth factor (PDGE) Raf (a protein kinase)... 

Steroid hormones act in a different manner from most hormones we have considered. In many cases, they do not bind to plasma membrane receptors, but rather pass easily across the plasma membrane. Steroids may bind directly to receptors in the nucleus or may bind to cytosolic steroid hormone receptors, which then enter the nucleus. In the nucleus, the hormone-receptor complex binds directly to specific nucleotide sequences in DNA, increasing transcription of DNA to RNA (Chapters 31 and 34). 

In addition to inhibiting cytokine synthesis by glucocorticoids, cytokine effects can be prevented by scavenging the cytokine either with neutralizing antibodies or soluble receptors or by blocking the respective cytokine plasma membrane receptors with blocking antibodies or receptor antagonists. 

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... 

The neurotransmitters of the ANS and the circulating catecholamines bind to specific receptors on the cell membranes of effector tissue. Each receptor is coupled to a G protein also embedded within the plasma membrane. Receptor stimulation causes activation of the G protein and formation of an intracellular chemical, the second messenger. (The neurotransmitter molecule, which cannot enter the cell, is the first messenger.) The function of intracellular second messenger molecules is to elicit tissue-specific biochemical events within the cell that alter the cell s activity. In this way, a given neurotransmitter may stimulate the same type of receptor on two different types of tissue and cause two different responses due to the presence of different biochemical pathways within each tissue. 

L The answer is a. (Hardman, pp 1460, 14642) Cosyntropin is related to adrenocorticotropin. It corresponds to the first 24 amino acids of adreno-corticotropin. Cosyntropin complexes with a plasma membrane receptor that brings about the activation of adenylyl cyclase. Adenylyl cyclase catalyzes the formation of cAMP from ATP In the cytoplasm, cAMP activates cAMP-dependent protein kinase, which participates in the phosphorylation of specific substrate proteins (e.g., enzymes). The phosphorylated protein eventually induces the particular response on the target cell. 

Multiple forms of heterotrimeric G proteins exist in the nervous system. Three types of heterotrimeric G protein were identified in early studies. G termed transducin, was identified as the G protein that couples rhodopsin to regulation of photoreceptor cell function (see Ch. 49), and Gs and G were identified as the G proteins that couple plasma membrane receptors to the stimulation and inhibition, respectively, of adenylyl cyclase, the enzyme that catalyzes the synthesis of cAMP (see Ch. 21). 

Membrane-bound forms of guanylyl cyclase act as plasma membrane receptors 368... 

A large number of cytokines generated during an inflammatory response can affect neutrophil function. Some of these cytokines, such as G-CSF and GM-CSF, can affect the rate of biosynthesis of mature neutrophils in the bone marrow they can also affect the function of mature cells by priming certain functions (such as the respiratory burst, degranulation and expression of some plasma membrane receptors). These effects are described in detail in Chapters 2 and 7, respectively the present chapter briefly describes some the properties of cytokines known to affect the function of mature neutrophils. 

Almost all receptor-mediated neutrophil functions are mediated via GTP-binding proteins (G-proteins), which provide the link between occupancy of plasma membrane receptors and the activation of intracellular enzymes, such as phospholipases and protein kinases. There are two groups of G-proteins those that are heterotrimeric and those with low molecular weight. 

REF%K Human gene for plasma membrane receptor REF%K GB X13556... 

Hicke, L. and Riezman, H. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cdl 1996, 84, 277-87. 

Hicke L (1999) Gettin down with ubiquitin turning off cell-surface receptors, transporters and channels. Trends Cell Biol 9 107-12 Hicke L, Riezman H (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84 277-287 Hicke L, Zanolari B, Riezman H (1998) Cytoplasmic tail phosphorylation of the a-factor receptor is required for its ubiquitination and internalization. J Cell Biol 141 349-358... 

Interferon alfa-2b (Intron A) is a recombinant DNA product derived from the interferon alfa-2b gene of human white blood cells. Its mechanism of antitumor action involves binding to a plasma membrane receptor but is otherwise poorly understood. Its serum half-life is 2 to 3 hours after parenteral administration. 

Calcitoifin interacts with specific plasma membrane receptors within target organs to initiate biological effects. This interaction has been directly finked to the generation of cAMP via adenylyl cyclase activation. 

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