Secretory granule

While the basic features of SNARE assembly and disassembly provide a convenient framework for explaining how membrane fusion works, both the regulation of SNAREs and the molecular details of fusion are not well understood. Most is known about the neuronal SNAREs that mediate regulated membrane fusion of synaptic vesicles and of secretory granules in neuroendocrine cells. They include synaptobrevin2, localized to the synaptic vesicle, and SNAP25 ( SNAPs) and syntaxinlA, both of which are localized to the plasma... 

Puri N. Roche PA Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms. Proc Natl Acad Sci USA 2008 105 2580-2585. 

Fig.1. Electron micrograph of a mast cell in human heart tissue. The cytoplasm contains numerous secretory granules. The mast cell is adjacent to a coronary blood vessel, surrounded by collagen fibers and close to a myocyte. Uranyl acetate and lead citrate stained. Orig. magnif. lO.OOOx. 

Proteoglycans are also found in intracellular locations such as the nucleus their function in this organelle has not been elucidated. They are present in some storage or secretory granules, such as the chromaffin granules of the adrenal medulla. It has been posm-lated that they play a role in release of the contents of such granules. The various functions of GAGs are summarized in Table 48-8. 

The recruitment of zinc for a structural role, or to activate an enzyme, has been observed. The zinc ion induces the dimerization of human growth hormone (hGH), with two Zn ions associated per dimer of hGH. This is confirmed by replacement of possible zinc binding residues resulting in weakened binding of the zinc ion. Formation of a zinc-hGH dimeric complex may be important for storage of hGH in secretory granules.975 In a toxic role, anthrax lethal factor is one of the three components of the secreted toxin and is a zinc-dependent protease that cleaves a protein kinase and causes lysis of macrophages.976... 

Protein/peptide hormones are derived from amino acids. These hormones are preformed and stored for future use in membrane-bound secretory granules. When needed, they are released by exocytosis. Protein/peptide hormones are water soluble, circulate in the blood predominantly in an unbound form, and thus tend to have short half-lives. Because these hormones are unable to cross the cell membranes of their target tissues, they bind to receptors... 

The catecholamines are biologically similar to protein/peptide hormones. These hormones are soluble in the blood and are transported in an unbound form. Therefore, the catecholamines have a relatively short half-life. Because these hormones do not cross cell membranes, they bind to receptors on the membrane surface. Finally, the catecholamines are stored intracellu-larly in secretory granules for future use. 

With regard to the response time of the gel, polyelectrolyte gels require seconds to minutes to deform in electric fields. Needless to say, the deformation speed depends on the thickness of the gel and the intensity of the applied field. In 1993, a fast-responsive gel was found by Nanavati and Fernandez. A secretory granule gel particle obtained from beige mice and having a diameter of 3 pm at negative potentials was transparent and swollen within milliseconds of the application of an electric field of 5000 V/cm [19]. 

Endo, B.Y. (1993) Ultrastructure of subventral gland secretory granules in parasitic juveniles of the soy bean cyst nematode, Heterodera glycines. Proceedings of the Helminthological Society of Washington 60, 22-34. 

Hussey, R.S. and Mims, C.W. (1990) Ultrastructure of esophageal glands and their secretory granules in the root-knot nematode Meloidogyne incognita. Protoplasma 156,9-18. 

Yano S, Kashima K, Daa T, et al. An antigen retrieval method using an alkaline solution allows immunoelectron microscopic identification of secretory granules in conventional epoxy-embedded tissue sections. /. Histochem. Cytochem. 2003 51 199-204. 

Proinsulin is proteolytically processed in the coated secretory granules, yielding mature insulin and a 34-amino acid connecting peptide (C peptide, Figure 11.1). The C peptide is further proteolytically modified by removal of a dipeptide from each of its ends. The secretory granules thus contain low levels of proinsulin, C peptide and proteases, in addition to insulin itself. The insulin is stored in the form of a characteristic zinc-insulin hexamer, consisting of six molecules of insulin stabilized by two zinc atoms. 

Figure 11.1 Proteolytic processing of proinsulin, yielding mature insulin, as occurs within the coated secretory granules...

A variety of methods have been developed to study exocytosis. Neurotransmitter and hormone release can be measured by the electrical effects of released neurotransmitter or hormone on postsynaptic membrane receptors, such as the neuromuscular junction (NMJ see below), and directly by biochemical assay. Another direct measure of exocytosis is the increase in membrane area due to the incorporation of the secretory granule or vesicle membrane into the plasma membrane. This can be measured by increases in membrane capacitance (Cm). Cm is directly proportional to membrane area and is defined as Cm = QAJV, where Cm is the membrane capacitance in farads (F), Q is the charge across the membrane in coulombs (C), V is voltage (V) and Am is the area of the plasma membrane (cm2). The specific capacitance, Q/V, is the amount of charge that must be deposited across 1 cm2 of membrane to change the potential by IV. The specific capacitance, mainly determined by the thickness and dielectric constant of the phospholipid bilayer membrane, is approximately 1 pF/cm2 for intracellular organelles and the plasma membrane. Therefore, the increase in plasma membrane area due to exocytosis is proportional to the increase in Cm. 

Interstitial nucleotides are derived from intracellular sources. In addition to its central role in cellular energy metabolism, ATP is a classical neurotransmitter that is packaged into secretory granules of neurons and adrenal chromafin cells and released in quanta in response to... 

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