China
Africa
Explore chapters and articles related to this topic
Intracellular Maturation of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Erik Fries, E. Mathilda Sjöberg
The mere assembly of amino acids into a polypeptide is not sufficient for the formation of an active protein. The newly synthesized polypeptide must also acquire a specific conformation and in many cases selected amino acid residues must undergo chemical modification. For secretory proteins, this maturation occurs during their transport from the site of synthesis to the surface of the cell. To understand the mechanisms of this process, it is necessary to recognize that the secretory pathway consists of a series of compartments and that each compartment contains a set of modifying enzymes. The first section of this chapter therefore deals with the compartmentation of the secretory pathway. In the remainder, we use acute phase proteins as examples to describe various modifications. The number of modifications that secretory proteins can undergo is large and only some of these have been found on acute phase proteins; readers who are interested in other modifications should consult References 1 and 2.
Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
All cells possess a constitutive secretory pathway whereby vesicles that originate in the Golgi complex contain newly synthesized proteins (i.e., enzymes, growth factors, receptors, and extracellular matrix components) and carry them to the cell surface. Once there, the vesicles contact the plasma membrane and either release their content to the cell exterior (e.g., hormones or neurotransmitters), or their enclosed proteins become embedded within the plasma membrane (e.g., receptors). Neurons and endocrine/neuroendocrine cells are highly specialized cells that are dedicated to intercellular communication and store their chemical signals in committed secretory vesicles. Upon receiving appropriate stimuli, these cells release their content to the cell exterior by a calcium-regulated exocytosis.
The rab Gene Family
Published in Juan Carlos Lacal, Frank McCormick, The ras Superfamily of GTPases, 2017
Armand Tavitian, Ahmed Zahraoui
Evidence for the role of GTP hydrolysis in vesicular traffic comes from studies in cell-free systems. These systems reconstitute vesicular traffic between different cellular compartments. They measure vectorial transport and/or fusion of vesicles with their acceptor membrane. Cell-free assays have shown that several steps of exocytic and endocytic membrane traffic in mammalian cells are sensitive to GTPγS. Along the secretory pathway, the slowly hydrolyzable GTP analog, GTPγS, irreversibly and dramatically inhibits transport between the endoplasmic reticulum (ER) and cis-Golgi compartment, and between successive cisternae of the Golgi stack.39-40 It also inhibits the recycling of the mannose 6-phosphate receptor through the trans-Golgi network (TGN).41 Recently, it has been shown that GTPγS blocks the transport of membrane proteins between TGN and plasma membrane (PM).42-43 In addition, GTPγS inhibits the formation of constitutive secretory vesicles and immature secretory granules.44
Efanesoctocog alfa for the prevention and treatment of bleeding in patients with hemophilia A
Published in Expert Review of Hematology, 2023
FVIII is a critical cofactor in the activation of coagulation FX by FIXa with subsequent thrombin generation and clot formation [13]. It is the product of a large gene (186 kb), the human sequence of which was reported in 1984 [14,15]. Factor VIII is synthesized in endothelial cells and has a large precursor protein of 2351 amino acids, including a 19 amino acid signal peptide [16,17]. Within the secretory pathway it is further processed to a heterodimer with conserved structural domains, including a B domain that is not needed for hemostatic function [18]. Following secretion greater than 95% of FVIII is bound to von Willebrand factor in circulation and released with FVIII activation by thrombin [19,20]. As a result, the half-life of FVIII in circulation is dependent on VWF and while there are several mediators of FVIII clearance, endogenous VWF binding-mediated clearance is a major factor [21,22]. Half-life of infused FVIII in patients with hemophilia varies with their underlying VWF levels [23].
Misrouting of glucagon and stathmin-2 towards lysosomal system of α-cells in glucagon hypersecretion of diabetes
Published in Islets, 2022
Farzad Asadi, Savita Dhanvantari
In islets from diabetic mice, the decrease in Stmn2 was accompanied by alterations in the trafficking of glucagon and Stmn2 through the late endosome-lysosome pathway, as indicated by the dramatic decrease in localization of glucagon and Stmn2 in Lamp2A+ lysosomes. These results are consistent with those from our previous study showing that siRNA-mediated depletion of Stmn2 sharply decreased the localization of glucagon in lysosomes and enhanced glucagon secretion. In the context of dynamic movements of cargos within the endolysosomal system, the late endosome cargos can be transported to the lysosome (anterograde) or the plasma membrane (retrograde). Therefore, we reasoned that diabetes-induced glucagon hypersecretion could occur through a switch from anterograde to retrograde transport. Retrograde transport can occur in two ways: i) to the early endosome, recycling endosome and then the plasma membrane, or ii) to the Golgi apparatus and then the secretory pathway.41,42 However, the lack of glucagon and Stmn2 localization in early endosomes and recycling endosomes suggests that retrograde transport toward the early endosome-recycling endosome may not occur in α-cells. Therefore, glucagon hypersecretion in diabetes could be a result of enhanced retrograde trafficking of glucagon and Stmn2 from the late endosome toward the TGN, and then through the regulated secretory pathway.
The role of SCAMP5 in central nervous system diseases
Published in Neurological Research, 2022
Ye Chen, Jiali Fan, Dongqiong Xiao, Xihong Li
In mammals, neurons, endocrine cells and exocrine cells all secrete proteins along the secretory pathway [17]. Genetics and in vitro experiments have revealed the molecular mechanism of exocytosis from neurons and from endocrine and exocrine cells. Innate immunity and adaptive immunity are regulated by cytokines, especially cytokines secreted by macrophages [18,19]. The membrane transport process during exocytosis and endocytosis is regulated by the SCAMP E peptide [20]. Previous studies on SCAMPs have mostly focused on the regulation of exocytosis during LDCV secretion or TGN vesicle transport. For example, SCAMP1 can promote the expansion and closure of fusion pores and participate in the regulation of LDCV secretion [21,22]. SCAMP2 interacts with phospholipase D1 and phosphatidylinositol diphosphate (PIP2) through its E peptide to regulate the formation of fusion pores during LDCV exocytosis [23].