Abnormal Intracellular Zinc Metabolism Caused By Disruption Of The Trpl1 Tmem163 Protein Interaction

​Cystic fibrosis is an inherited, chronic disease of the secretory glands which directly affects the lungs and digestive system (NLM, 2015). To look more closely at a cellular level, there is a defective gene in which their protein product that regulates movement of sodium

Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductor regulator (CFTR) gene, which codes for the CFTR protein (Sartin, 2013). The CFTR protein is a chloride channel present in secretory glands and the epithelial cells of numerous organs. Due to the high affinity of chloride, sodium and water, CFTR protein plays a vital role in the homeostatic

Cystic Fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) which is located in the middle of chromosome 7. The CFTR gene encodes a protein of the same name. This protein functions as a “channel across the membrane of cells that produce mucus, sweat, saliva, tears and digestive enzymes” (Genetics Home Reference, 2015). The channel transports chloride ions which are negatively charged particles, in and out of cells which help in controlling the water movement in tissues to allow for the production of thin, feely flowing mucus, a substance that lubricates and lines the airways, digestive system, reproductive system and other tissues and

Cystic fibrosis (CF), is an autosomal recessive disorder [figure 1.], caused by a mutation in two genes on chromosome 7 – the genes responsible for the way water and salts pass in and out of the cells in the body. CF affects the secretion and reabsorption of chloride ions, producing a much thicker than normal layer of mucus (in the lungs, pancreas and liver primarily) that is ideal for bacteria and infection to flourish. The faulty gene may fail to produce the cystic fibrosis transmembrane conductance regulator (CFTR) protein or may produce the protein however this protein is faulty is such a way that it does not regulate chloride secretion and reabsorption properly or at all. Currently there are a wide array of

Cystic Fibrosis is caused by a genetic defect in Chromosome 7. Chromosome 7 encodes the cystic fibrosis transmembrane conductance regulator, also known as CFTR. There are over 1,000 mutations of this gene causing cystic fibrosis, with each mutation manifesting as a different variation of disease onset and clinical presentation. The most common mutation is the loss of phenylalanine residue at deltaF508. The abnormal functioning CFTR causes impaired chloride transport and more viscous secretions. The defect causes dehydrated secretions in the respiratory tract and gastrointestinal tract. Being dehydrated, these secretions become more difficult to move throughout the body. Along with impaired mucociliary clearance, this leads to chronic infection and inflammation, which in turn leads to more impaired mucociliary clearance. It unfortunately becomes an endless

Cystic fibrosis (CF) is a progressive condition in which epithelial exocrine glands are obstructed (Howe, 2001). Whilst many organs and bodily systems are disrupted by CF, the lungs and gastrointestinal organs are predominantly affected; it is also most common amongst the Caucasian population due to the autosomal recessive gene (Quitter et al., 2003 cited in Wolfe & Mash, 2006, pg 514). The faulty gene effects the production of cystic fibrosis transmembrane conductance regulator protein, which is responsible for the formation of molecular tunnels which monitor the movement of salts and water from the cells (Hopkin, 2010 pg 4).

The Cystic Fibrosis Gene codes for a protein called cystic fibrosis transmembrane conductance regulator produced in the epheilial cells. The CFTR protein acts as channel in the membrane of cells that produce mucus, sweat, saliva, tears, and digestive system. This channels transport chloride ions in and out of the cell, because the chloride ions help control the movement of water in the tissue of the human body, in a process called diffusion. This process necessary to the production of mucus, mucus is a slippery substance that lubricates and protects the lining of the lung airways, digestive systems, reproductive systems, and organs and tissues. However, when a person inherits mutated CFTR gene,

Cystic fibrosis is a recessive genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This mutation causes problems with the apical membrane CFTR protein which when working to its full potential regulates the sodium and chloride intake in epithelial cells (Eitan Kerem et al. 2005). It affects about 70,000 people in the world and in the UK it is said to affect 1 in every 2,500 children. The disease causes the apical membrane CFTR protein to not be able to transport the sodium and chloride it needs to, this can have a huge effect on multiple organ systems, mainly the respiratory system. The most common clinical problems Cystic Fibrosis causes are pulmonary damage

Cystic fibrosis is an Autosomal Recessive Disorder. The mutation of the Cystic Fibrosis Transmembrane Regulator is what causes Cystic Fibrosis. Normally, in the cells, CFTR protein is a channel that allows cells to release chloride and other ions. In the case of an individual with Cystic Fibrosis, the protein is defective therefore cells do not release the chloride. For that reason, there is a thick, sticky mucus with individual with cystic fibrosis.

Stemming from a genetic mutation with a membrane pore, or channel that helps to facilitate the transport of bicarbonate electrolytes and chloride from between the inside and the outside of the cell, cystic fibrosis and its inherent symptoms are caused by the loss of the pore channel, which results in inflammation and mucus accumulation. Dehydration of the cell surface also occurs. Normally, cells have a cystic fibrosis transmembrane regulator channel that influences fluid secretion in epithelial cells. When this channel is mutated, there is a decrease in the flow of ions and water, and this results in dehydrated mucous that affects breathing. This in turn causes lethal bacterial infections by blocking ducts within the lungs. The most common mutation of the cystic fibrosis conductance regulator is F508del-CFTR. This mutation creates a misprocessed protein that rapidly degrades as it is abnormally retained in the endoplasmic reticulum compartment, therefore making it absent in the plasma membrane

Cystic Fibrosis (CF) is an autosomal recessive gene that causes a wide range of symptoms because there are over 1,000 changes or mutations that can occur within the cystic fibrosis transmembrane receptor (CFTR) protein. The CFTR protein is generally a chloride ion chain “regulated by cyclic adenosine monophosphate and therefore can act as a regulator of other electrolyte channels”(Grossman, S., & Grossman, L. 2005, p. 46). Typically this protein allows chloride ions to exit mucus-producing cells allowing water to flow in and thin the mucus. However, if the CFTR protein has been mutated, such as in cystic fibrosis, chloride ions cannot exit. This causes the mucus to thicken, become sticky, and obstruct the various channels it passes through. This build up of mucus also prevents bacteria from being cleaned from cells thoroughly increasing the patients risk for infections (Grossman, S., & Grossman, L. 2005). However, the severity of CF depends on whether the patients have complete or partial loss of the CFTR gene. If the person has the classic form of CF abnormalities of CFTR will commonly affect “…the respiratory, gastrointestinal, endocrine and metabolic, and genitourinary systems”(Schram, C. 2012). However, if people have atypical forms of CF their genetic disorder may only affect one of the organ systems and may not be found until the patient develops symptoms in their late childhood, early adolescence, or adulthood

Chloride channels are a structurally diverse superfamily of transmembrane proteins that facilitate the transport of negative anions across the cell membrane. These channels are involved in a plethora of physiological processes such as neurotransmission, excitation of skeletal, cardiac, and smooth muscle, salt transport, cell volume regulation, and acid production in internal and external compartments. Families of these channels include the voltage-gated CLC family, calcium-activated CaCC family, GABAA receptors, glycine receptors, and the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an ATP-binding cassette (ABC) transporter that is responsible for proper fluid transport across the epithelial membrane of various cells within body tissues such as the lungs, liver, digestive tract, and reproductive tract. Mutations in the protein sequence of CFTR are characteristic of the disease cystic fibrosis, a disease where improper or absent ion movement decreases the flow of water across exocrine epithelial cells causing mucus and other secretions to be unusually thick.

Purpose of the Study: Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR)1 is responsible for cystic fibrosis (CF), an inherited multisystem disease characterized by progressive deterioration in lung function and pancreatic insufficiency. CFTR appears to act as a negative modulator of inflammation2, both under basal conditions and in the presence of inflammatory triggers such as lipopolysaccharide derived from Pseudomonas aeruginosa, the major cause of morbidity and mortality in CF3-5. Compounds that either potentiate CFTR function by increasing the time that chloride channels are open (VX-770) or enhance cellular processing and delivery of CFTR to the cell membrane (VX-809) may therefore augment the immune response as the quantity and function of CFTR increase.

Nuclear Lamina is a mesh like network that lines the nuclear membrane and provides architectural support 2. Lamin proteins are important for cellular structure as well as cellular organization and because of this, functioning lamin proteins are vital in proper expression of genes 1. When mutated, lamin proteins lead to multiple degenerative diseases related to premature aging and diseases like progeria and muscular dystrophy. Although comprehensive research has been done on mutant lamin proteins, the relationship between genotypes and phenotypes are poorly understood 2. This proposal aims to analyze the different genotypic and phenotypic effects by

The defective cell organelle is the endoplasmic reticulum. Cystic fibrosis occurs due to a mutant gene known as CTFR. Instead of the CTFR protein being threaded and translated, it get stuck in the endoplasmic reticulum, causing the cell to lose its permeability. Eventually, salts starts building up outside the cells since they cannot pass through.