Mouse Knockout Models of Biliary Epithelial Cell Formation and Disease
Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso in The Pathophysiology of Biliary Epithelia, 2020
ATP8B1 encodes a P/type ATPase that is mutated in benign intrahepatic cholestasis (BRIC) as well as familial intrahepatic cholestasis (FIC1) The mice have a milder hepatic phenotype due to abnormalities in trans location of aminophospholipids between membrane leaflets resulting in aberrant intestinal bile salt absorption. Also known as BSEP (bile salt export protein), and SPGP (sister for P/glycoprotein), ABCBl 1 is an ATP/dependent membrane transporter expressed in the canalicular membrane of hepatocytes that functions in transporting bile acids out of hepatocyte into the canaliculus. Mouse mutants (or ABCB1 1 show mild cholestasis, reduced hepatic bile acid output and high amounts of tetra hydroxylated bile acids suggesting an alternative protective mechanism for bile acid export. 50–52
Neurological Disease
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
This is a rare autosomal recessive disorder of copper metabolism due to mutations in the gene encoding ATP7B, a copper transporting-P-type ATPase. Patients may present with liver disease in childhood or with the neurological syndrome in adolescence. Neurological symptoms include impaired concentration, declining intellect, behavioural problems, involuntary movements and generalized dystonia, ataxia or an akinetic–rigid syndrome. Patients have a typical smiling facial appearance with drooling and often have slurred speech. There may be copper deposition in Descemet's membrane of the cornea, giving a greenish brown pigmentary (Kayser–Fleischer) ring, which may only be visible at slit-lamp examination.
Non-viral liver disease
Michael JG Farthing, Anne B Ballinger in Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Wilson’s disease, or hepatolenticular degeneration, is a rare autosomal disorder of copper accumulation.73 The Wilson’s gene is located on chromosome 13 and encodes a copper-transporting P-type ATPase protein.74, 75 Deficiency of the gene product is likely to be responsible for the lack of copper incorporation into caerulo-plasmin and the defective biliary excretion of copper seen in Wilson’s disease. This results in excess copper accumulation in the liver, brain and other organs including the kidney and cornea, resulting in Kayser-Fleischer rings (a golden-brown or greenish discoloration in the limbic area seen best during slit-lamp examination). The copper accumulation eventually leads to tissue damage.
Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles
Published in Journal of Extracellular Vesicles, 2020
Javier Mariscal, Tatyana Vagner, Minhyung Kim, Bo Zhou, Andrew Chin, Mandana Zandian, Michael R. Freeman, Sungyong You, Andries Zijlstra, Wei Yang, Dolores Di Vizio
Detailed analysis of the palmitoylated proteins involved in these biological processes revealed that, while the differentially enriched proteins in L-EVs were mostly represented by cytoplasmic proteins involved in cell growth (GSN, FSCN1 and ATCR3) and signal transduction (ANXA1, ARF1, ROCK2 and CORO1B); the proteins enriched in S-EVs were mainly represented by two major groups of plasma membrane proteins (Figure 3(c)). The first group contained two families of transmembrane palmitoyl-proteins with transporter activity: the P-type ATPase superfamily (ATP1A1, ATP1B1 and ATP2B1) and the cation transporters (SLC12A2, SLC39A6 and SLC46A1). The second group contained palmitoyl-proteins associated with signal transduction and cell communication (ANXA6, LPAR1, GNB1, LYN, NTSR1, OXTR and STX4) (Figure 3(c)).
Awareness and current knowledge of Parkinson’s disease: a neurodegenerative disorder
Published in International Journal of Neuroscience, 2019
Asmat Ullah Khan, Muhammad Akram, Muhammad Daniyal, Rida Zainab
The accurate part of autophagy in the pathogenesis of PD is unclear [133]. However, there are some evidences which suggest that autophagy plays a role in PD pathology. The variation in the normal process of autophagy leads towards neurodegeneration and cause motor dysfunctions [134]. In addition, lysosomes in their membranes contain proteins called P-type ATPase (PARK9), which play role in degradation of protein molecules [135]. Defects in autophagy cause dopaminergic neuronal loss in SN during motor neuron disorder, in which the autophagosomes are unable to bind with lysosomes [136]. Mutation in alpha-synuclein binds to the CMA receptors, which then causes toxicity by altering the normal functions of these receptors, leads towards proteins aggregation. Macro-autophagy and UP system play a role in degradation of this vulnerable alpha-synuclein [137]. Moreover, different studies showed that alteration in the normal mechanism of autophagy cause neurodegeneration and cell death [138].
Metal-metal interaction and metal toxicity: a comparison between mammalian and D. melanogaster
Published in Xenobiotica, 2021
Xiaoyu Yu, Xianhan Tian, Yiwen Wang, Chunfeng Zhu
Although DMT1 can absorb Cu2+, copper transporter 1 (Ctr1) is the main absorption mechanism in mammals. Three high-affinity homologs, Ctr1A, Ctr1B, and Ctr1C have been identified in the fruit fly (Zhou et al.2003, Petris 2004). Ceruloplasmin in blood transports Cu2+ to the reductase on the surface of the cell membrane and reduces it to Cu+, which is then transferred by Ctr1 on the membrane (Espinoza et al.2012). Cu entering cells can bind to Cu-specific chaperones such as COX17, CCS, and ATOX1, which can be further transported to cytochrome c oxidase in mitochondria (Banci et al.2008)(copper chaperones for superoxide dismutase) SOD1 (Schmidt et al.2000) and ATP7A. ATP7A also transports Pb out of cells. However, at present, there is only one Cu P-type ATPase transporter called ATP7 in D. melanogaster, which is expressed widely (Norgate et al.2006). Its function is similar to ATP7A and can transfer Cu to the secretory pathway or to the circulatory system through intestinal cells (Burke et al.2008).
Related Knowledge Centers
- Archaea
- Aspartic Acid
- Atpase
- Bacteria
- Eukaryote
- Flippase
- Phospholipid
- Phosphorylation
- Active Transport
- Adenosine Triphosphate