CD BioGlyco provides comprehensive and deep insights into disorders of vesicular trafficking. We believe these insights will help you in your research.
Decades of research have shown that gene mutations may lead to misfolding and aggregation of mutant proteins. Such aggregates are most commonly found in the endoplasmic reticulum (ER). Aberrant protein modification processes may also lead to intracellular protein mislocalization prevalent in inherited diseases such as congenital disorders of glycosylation (CDG).
In hereditary human diseases, protein mislocalization is caused by mutations in genes directly involved in vesicular transport. Vesicle transport is the process by which membrane-bound vesicles ("carriers") are released from a donor compartment and moved to a specific cellular location (an acceptor site). Upon arrival at the acceptor, the carrier membrane fuses with the membrane of the target organelle and transports its contents to its destination.
Fig.1 Vesicular transport. (Gissen & Maher, 2007)
Diseases associated with membrane transport defects are concentrated in virtually all tissues and organ systems, some affecting multiple systems, while others are restricted to one tissue type or organ. Diseases are most often caused by mutations that result in the expression or loss of function of components of the transport machinery, but some are also caused by toxic gain-of-function mutations. Diseases due to defects in transport machinery can be developmental or can occur during the lifespan, usually manifesting during the aging process.
Major neurodegenerative diseases are closely associated with membrane traffic defects, particularly in the endosomal system. Genetic association studies have linked variants or altered expression levels of phosphatidylinositol-binding clathrin assembly protein, bridging integrator 1/amphiphysin 2, cortactin-CD2-associated protein, and synaptojanin (a component of lattice protein-mediated cytokinesis), to the risk of developing Alzheimer's disease.
Membrane traffic is essential for innate and adaptive immunity. For example, mediating phagocytosis of invading microorganisms, supporting the biosynthesis and signaling of many receptors found on immune cells, and facilitating the secretion of antibodies, cytokines, and other immunomodulatory factors. Thus, a number of immune diseases, including immunodeficiencies and autoimmune diseases, can be attributed to defective membrane trafficking. These include familial phagocytic lymphohistiocytosis, an immune disease caused by mutations in protein unc-13 homolog D, syntaxin 11, or syntaxin binding protein 2. These proteins control T cell and natural killer (NK) cell immune synapses and platelet lysis granule release granule cytokinesis. As a result, cells with these mutations have an impaired ability to mediate cellular killing, leading to over-activation of the immune system.
Defective transport in the secretory and endocytic pathways can affect enterocyte function and lead to intestinal disease. Enterocytes absorb fats from the intestine and pack them into celiac particles, which are formed in the ER and secreted into the bloodstream.
CDG is associated with a system that transports components between the ER and the Golgi apparatus. This transport system is known as vesicular transport. In this system, vesicles are required to shuttle different components of glycosylation, such as enzymes and proteins, between the ER and the Golgi apparatus. In addition, the Golgi consists of different compartments, which allow for different types of glycan modifications to occur in different parts of the Golgi, and vesicles are used to transport substances between these subcompartments of the Golgi.
Vesicles can be surrounded by coat protein complexes. Vesicles can attach to the Golgi membrane by using different proteins, such as the conserved oligomeric Golgi (COG) complex, SNARE, and binding proteins, and CDGs are associated with defects in many of these proteins.
| Disorders of vesicular trafficking | ||||
|---|---|---|---|---|
| COG1-CDG | COG2-CDG | COG4-CDG | COG5-CDG | COG6-CDG |
| COG7-CDG | COG8-CDG | GORAB-CDG | GOSR2-CDG | SEC23B-CDG |
| TRAPPC9-CDG | TRAPPC11-CDG | TRIP11-CDG | VPS13B-CDG | STX5-CDG |
Here we describe one of the disorders in the Disorders of Multiple Glycosylation and Other Pathways. A full understanding of this information is helpful for the development of relevant research. As the partner of customers, CD BioGlyco provides comprehensive services including but not limited to Custom Complex N-linked Oligosaccharides Synthesis, Custom Glycosylation of Cell Membranes, Custom Glycosylation of Bacteria Membranes, Characterization of Glycosylation in Fc-Fusion Protein Drugs, and Characterization of Glycosylation in Protein Drugs. We also provide other high-quality custom services to meet the individual needs of customers. If you are interested in our services, please contact us for more details without any hesitation.
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