Secretion, exocytosis

Constitutive exocytosis/secretion takes place in all eukaryotic cells and is essential for cell viability and growth. Trafficking vesicles destined for constitutive exocytosis originate from the trans-Golgi-network and contain secretory macromolecules derived from the... 

Calcium channels (Cay channels) mediate calcium influx in neuronal cells in response to membrane depolarisation, mediating a wide range of intracellular processes such as activation of calcium-dependent enzymes, gene transcription, and neurotransmitter exocytosis/secretion. Their activity is an essential requirement for the coupling of electric signals in the neuronal plasma membrane to physiological events within the cells. Biochemical characterisation of native brain Cay channels revealed that, in addition to the large principal... 

The formation of a platelet aggregate requires the recruitment of additional platelets from the blood stream to the injured vessel wall. This process is executed through a variety of diffusible mediators which act through G-protein-coupled receptors. The main mediators involved in this process are adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin (factor Ila). These mediators of the second phase of platelet activation are formed in different ways. While ADP is secreted from platelets by exocytosis, the release of TXA2 follows its new formation in activated platelets. Thrombin can be formed on the surface of activated platelets (see Fig. 2). 

Neutrophils represent an ideal system for studying osmotic effects on exocytosis. Stimulation of cytochalasin-B-treated neutrophils with the chemotactic peptide Jlf-formylmethionyl-leucyl-phenyl-alanine (FMLP) results in a rapid compound exocytosis up to 80% of lysosomal enzymes are released within 30 s (9-14). Secretion appears to be triggered by a rise in the level of cytosolic free calcium (15-18) promoted in part by entry of extracellular calcium through receptor-gated channels and in part by release of calcium that is sequestered or bound at some intracellular site (19-21). In this presentation, we augment our previously published data (22,23), which demonstrates that lysosomal enzyme release from neutrophils is inhibited under hyperosmotic conditions and that the rise in cytosolic calcium preceding secretion is inhibited as well. 

Logan MR, Odemuyiwa SO, Moqbel R Understanding exocytosis in immune and inflammatory cells the molecular basis of mediator secretion. J Allergy Clin Immunol 2003 111 923-932. 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Vesicular proteins and lipids that are destined for the plasma membrane leave the TGN sorting station continuously. Incorporation into the plasma membrane is typically targeted to a particular membrane domain (dendrite, axon, presynaptic, postsynaptic membrane, etc.) but may or may not be triggered by extracellular stimuli. Exocytosis is the eukaryotic cellular process defined as the fusion of the vesicular membrane with the plasma membrane, leading to continuity between the intravesicular space and the extracellular space. Exocytosis carries out two main functions it provides membrane proteins and lipids from the vesicle membrane to the plasma membrane and releases the soluble contents of the lumen (proteins, peptides, etc.) to the extracellular milieu. Historically, exocytosis has been subdivided into constitutive and regulated (Fig. 9-6), where release of classical neurotransmitters at the synaptic terminal is a special case of regulated secretion [54]. 

The constitutive pathway has not been studied as intensively as regulated secretion [54]. In particular, relatively little is known about targeting and regulatory mechanisms for these transport vesicles. Clathrin seems not to be directly involved in the constitutive secretory pathway. Antibodies that disrupt clathrin assembly in vitro inhibit endocytosis, but constitutive exocytosis is not affected [63]. 

Secretory cells, including neurons, also possess a specialized regulated secretory pathway. Vesicles in this pathway have soluble proteins, peptides or neurotransmitters stored and concentrated within secretory vesicles. At that point, these vesicles are actively transported to a site for extracellular delivery in response to a specific extracellular signal. Exocytosis through regulated secretion accomplishes different functions, including the... 

Eberhard, D. A., Cooper, C. L., Low, M. G. and Holz R. W. Evidence that the inositol phospholipids are necessary for exocytosis loss of inositol phospholipids and inhibition of secretion in permeabilized cells caused by a bacterial phospholipase C and removal of ATR Biochem. J. 268 15-25, 1990. 

Release is another area of difference conventional neurotransmitters are secreted from small synaptic vesicles (SSVs) after cytosolic [Ca2+] transiently reaches concentrations of 50-100 pmol/1, while peptides are released from LDCVs at lower concentrations of cytosolic [Ca2+] (Fig. 18-3). Conventional neurotransmitter release is thought to occur very close to the site of Ca2+ entry (see Chs 9,10), while neuropeptides are typically released at a distance from the site of Ca2+ entry (Fig. 18-4). Furthermore the Ca2+ that stimulates exocytosis from LDCVs may come from either internal stores or the extracellular fluid. Thus, the location of LDCVs relative to the site of Ca2+ influx has a very crucial impact on the intensity of stimulation necessary for secretion to occur. 

Somatostatin (SOM), initially identified by its ability to inhibit the release of growth hormone, is known to have inhibitory effects on a variety of cells [ 109], In mast cells and in basophils, SOM, like NT, has inhibitory as well as stimulatory effects depending on the concentration used. At high concentrations (> 10 8 M), SOM is a powerful stimulus of peritoneal mast-cell secretion (from both normal and athymic rats) and resembles other non-immunologic secretagogues such as compound 48/80, SP and NT in that it triggers a rapid exocytosis that is primarily dependent on cellular Ca [ 110,111], A similar effect is seen in vivo when injected into skin or skin blisters at high concentrations (> 10-8 M), SOM causes a rapid, dose-dependent release of histamine [88, 112] but when used at concentrations lower than those which elicit a secretory... 

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