Homeostasis of Dopamine
Nira Ben-Jonathan in Dopamine, 2020
This chapter provides an overview of the fundamental processes that govern dopamine (DA) homeostasis: synthesis, metabolism, release, reuptake, and storage. At any given time, DA homeostasis is determined by multiple complementary processes that are tightly regulated and well-coordinated. Catecholamine biosynthesis involves several sequential enzymatic reactions, with tyrosine hydroxylase (TH) serving as the rate-limiting step. Metabolic degradation is carried out primarily by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT), with additional glucuronidation and sulfation reactions. Within the producing cells, DA is stored in secretory vesicles whose main function is to protect it from degradation and enable its regulated release by a calcium-dependent exocytosis. Several types of transporters-the dopamine transporter (DAT), the vesicular monoamine transporters (VMATs), and organic cation transporters (OCTs)-are involved with the termination of the action of released DA through reuptake mechanisms and repackaging into the secretory granules. The different cytoarchitecture of DA within the "closed system" of the brain and the "open system" of the periphery necessitates several modifications of the fundamental processes of synthesis, metabolism, storage, transport and release of peripheral DA.
Blocks to polyspermy and the cortical granule reaction
Frank J. Longo in Fertilization, 2020
To prevent the lethal effects of polyspermy, specific mechanisms, or blocks to polyspermy, have evolved to allow only one sperm to enter the ovum or to participate in the development of the embryonic genome. A similar situation has also been described for mammalian oocytes: mouse germinal vesicle oocytes are not competent to establish a block to polyspermy and undergo cortical granule exocytosis. Energy is required to fill the stores, since depletion of ATP blocks the cortical granule reaction and there is an ATP-dependent binding of calcium-45 in isolated cortices. Peroxide is also toxic to sperm and in addition to hardening the fertilization membrane this system may provide an additional block to polyspermy. Cortical granule content from sea urchins, amphibians and mammals has been examined directly by biochemical and cytochemical techniques and indirectly by analysis of the medium following their discharge.
Secretion
Stephen Rothman in Proteins Crossing Membranes, 2019
A mindset similar to that for the microvesicles was at work for the mechanism of secretion itself. In the mid-19th century, the great German microscopic anatomist Rudolf Heidenhain noticed that under certain circumstances when pancreatic secretion was stimulated, the area of the acinar cell occupied by zymogen granules was markedly decreased. In the minds of many, and in many research papers, its presence was seen jointly both as proof of exocytosis and proof that this was the mechanism of secretion. The duct-facing surface of the acinar cell where the secretion of digestive enzymes into the intestines took place was not littered with omega figures as one might expect, especially in actively secreting glands. At another symposium, the creator of the vesicle model and soon-to-be Nobel Laureate gave a talk similar to mine about the mechanism of secretion by the acinar cell of the pancreas.
The Roles of Lysosomes in Inflammation and Autoimmune Diseases
Published in International Reviews of Immunology, 2015
Wei Ge, Dongxu Li, Yanpan Gao, Xuetao Cao
Lysosomes perform a range of functions, some of which, such as degradation, are common to all cell types. Others, such as secretion or lysosomal exocytosis, are more specialised and tend to involve fusion of this organelle with the cell surface to release its contents. This review describes lysosomal regulation of the inflammatory glucocorticoid signaling pathways, and summarizes the roles of lysosomes in negatively or positively modulating the production of inflammatory cytokines. We also review the characteristic changes in lysosomal hydrolases and membrane proteins in common autoimmune diseases. Finally, future directions in lysosome research are proposed, with it being suggested that the role of lysosomes will continue to be of growing interest in immunity research.
Mast cell transcriptome elucidation: what are the implications for allergic disease in the clinic and where do we go next?
Published in Expert Review of Clinical Immunology, 2014
Magda Babina, Efthymios Motakis, Torsten Zuberbier
Mast cells (MCs) are principal effector cells of type-I-allergic reactions but still poorly defined in humans. The consortium Functional Annotation of the Mammalian Genome 5 has created a map of body-wide transcriptome data for a multitude of human cell types, including MCs. MCs were found to have a surprising transcriptional landscape expressing a range of genes not (or barely active) elsewhere in the body. Whereas several MC specific genes have no annotated function, others belong to networks defining specific MC traits and functions, such as granule architecture, IgER signaling, exocytosis and mediator production. Several of these genes are so highly enriched in MCs (versus all other cells), that they appear potentially specific targets for therapeutic interventions in diseases in which MCs are actively involved. We present some interesting candidates, highlight the uniqueness of MCs and discuss their role in allergy and itch sensation based on these renewed insights.
Nanobodies reveal an extra-synaptic population of SNAP-25 and Syntaxin 1A in hippocampal neurons
Published in mAbs, 2019
Manuel Maidorn, Aurélien Olichon, Silvio O. Rizzoli, Felipe Opazo
Synaptic vesicle fusion (exocytosis) is a precisely regulated process that entails the formation of SNARE complexes between the vesicle protein synaptobrevin 2 (VAMP2) and the plasma membrane proteins Syntaxin 1 and SNAP-25. The sub-cellular localization of the latter two molecules remains unclear, although they have been the subject of many recent investigations. To address this, we generated two novel camelid single domain antibodies (nanobodies) specifically binding to SNAP-25 and Syntaxin 1A. These probes penetrated more easily into samples and detected their targets more efficiently than conventional antibodies in crowded regions. When investigated by super-resolution imaging, the nanobodies revealed substantial extra-synaptic populations for both SNAP-25 and Syntaxin 1A, which were poorly detected by antibodies. Moreover, extra-synaptic Syntaxin 1A molecules were recruited to synapses during stimulation, suggesting that these are physiologically-active molecules. We conclude that nanobodies are able to reveal qualitatively and quantitatively different organization patterns, when compared to conventional antibodies.
Related Knowledge Centers
- Plasma Membrane
- Secretory Vesicles
- Synaptic Vesicle
- Cell Membrane
- Endocytosis
- Post
- Translational Modifications