Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The G protein-coupled V(2) vasopressin receptor is crucially involved in water reabsorption in the renal collecting duct. Mutations in the human V(2) vasopressin receptor gene cause nephrogenic diabetes insipidus. Many of the disease-causing mutants are retained intracellularly by the quality control system of the early secretory pathway. It was previously thought that quality control system is restricted to the endoplasmic reticulum (ER). Here, we have examined the retention mechanisms of eight V(2) vasopressin receptor mutants. We show that mutants L62P, DeltaL62-R64 and S167L are trapped exclusively in the ER. In contrast, mutants R143P, Y205C, InsQ292, V226E and R337X reach the ER/Golgi intermediate compartment (ERGIC) and are rerouted to the ER. The ability of the mutant receptors to reach the ERGIC is independent of their expression levels. Instead, it is determined by their folding state. Mutant receptors in the ERGIC may be sorted into retrograde transport vesicles by an interaction of an RXR motif in the third intracellular loop with the coatomer complex I. Our data show that disease-causing mutants of a particular membrane protein may be retained in different compartments of the early secretory pathway and that the folding states of the proteins determine their retention mechanism.
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PMID:Disease-causing V(2) vasopressin receptors are retained in different compartments of the early secretory pathway. 1552

Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord. Finding key mRNAs is important for improving repair after nerve injury. This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis. The left sciatic nerve denervation model was established in C57BL/6 mice. The left L4-6 spinal cord segment was obtained at 0, 1, 2, 4 and 8 weeks after severing the sciatic nerve. mRNA expression profiles were generated by RNA sequencing. The sequencing results of spinal cord mRNA at 1, 2, 4, and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis. We identified 1915 differentially expressed mRNAs in the spinal cord, of which 4, 1909, and 2 were differentially expressed at 1, 4, and 8 weeks after sciatic nerve injury, respectively. Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury. These mRNAs were associated with the cellular response to lipid, ATP metabolism, energy coupled proton transmembrane transport, nuclear transcription factor complex, vacuolar proton-transporting V-type ATPase complex, inner mitochondrial membrane protein complex, tau protein binding, NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity. Of these mRNAs, Sgk1, Neurturin and Gpnmb took part in cell growth and development. Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption, oxidative phosphorylation and collecting duct acid secretion. Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development. Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different. The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury. These results provide reference data for finding new targets for the treatment of peripheral nerve injury, and for further gene therapy studies of peripheral nerve injury and repair. The study procedures were approved by the Ethics Committee of the Peking University People's Hospital (approval No. 2017PHC004) on March 5, 2017.
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PMID:Temporal changes in the spinal cord transcriptome after peripheral nerve injury. 3196 Aug 25