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Hassan Y. Naim - One of the best experts on this subject based on the ideXlab platform.
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a glutamine to proline exchange at amino acid residue 1098 in sucrase causes a temperature sensitive arrest of sucrase isomaltase in the endoplasmic reticulum and cis golgi
Journal of Biological Chemistry, 2003Co-Authors: Marcus J Propsting, Ralf Jacob, Hassan Y. NaimAbstract:Abstract A striking feature of phenotype II in congenital sucrase-isomaltase deficiency is the retention of the brush border protein sucrase-isomaltase (SI) in the cis-Golgi. This Transport Block is the consequence of a glutamine to proline substitution at amino acid residue 1098 of the sucrase subunit. Here we provide unequivocal biochemical and confocal data to show that the SIQ/P mutant reveals characteristics of a temperature-sensitive mutant. Thus, correct folding, competent intracellular Transport, and full enzymatic activity can be partially restored by expression of the mutant SIQ/P at the permissive temperature of 20 °C instead of 37 °C. The acquisition of normal trafficking and function appears to utilize several cycles of anterograde and retrograde steps between the endoplasmic reticulum and the Golgi implicating the molecular chaperones calnexin and heavy chain-binding protein. The data presented in this communication are to our knowledge the first to implicate a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder.
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a glutamine to proline exchange at amino acid residue 1098 in sucrase causes a temperature sensitive arrest of sucrase isomaltase in the endoplasmic reticulum and cis golgi
Journal of Biological Chemistry, 2003Co-Authors: Marcus J Propsting, Ralf Jacob, Hassan Y. NaimAbstract:A striking feature of phenotype II in congenital sucrase-isomaltase deficiency is the retention of the brush border protein sucrase-isomaltase (SI) in the cis-Golgi. This Transport Block is the consequence of a glutamine to proline substitution at amino acid residue 1098 of the sucrase subunit. Here we provide unequivocal biochemical and confocal data to show that the SI(Q/P) mutant reveals characteristics of a temperature-sensitive mutant. Thus, correct folding, competent intracellular Transport, and full enzymatic activity can be partially restored by expression of the mutant SI(Q/P) at the permissive temperature of 20 degrees C instead of 37 degrees C. The acquisition of normal trafficking and function appears to utilize several cycles of anterograde and retrograde steps between the endoplasmic reticulum and the Golgi implicating the molecular chaperones calnexin and heavy chain-binding protein. The data presented in this communication are to our knowledge the first to implicate a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder.
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Congenital sucrase-isomaltase deficiency - Identification of a glutamine to proline substitution that leads to a Transport Block of sucrase-isomaltase in a Pre-Golgi compartment
The Journal of clinical investigation, 1996Co-Authors: J. Ouwendijk, C.e.c. Moolenaar, Wilma Peters, Cornelis P. Hollenberg, L.a. Ginsel, Jack A. M. Fransen, Hassan Y. NaimAbstract:Congenital sucrase-isomaltase deficiency is an example of a disease in which mutant phenotypes generate Transport-incompetent molecules. Here, we analyze at the molecular level a phenotype of congenital sucrase-isomaltase deficiency in which sucrase-isomaltase (SI) is not Transported to the brush border membrane but accumulates as a mannose-rich precursor in the endoplasmic reticulum (ER), ER-Golgi intermediate compartment, and the cis-Golgi, where it is finally degraded. A 6-kb clone containing the full-length cDNA encoding SI was isolated from the patient's intestinal tissue and from normal controls. Sequencing of the cDNA revealed a single mutation, A/C at nucleotide 3298 in the coding region of the sucrase subunit of the enzyme complex. The mutation leads to a substitution of the glutamine residue by a proline at amino acid 1098 (Q1098P). The Q1098P mutation lies in a region that is highly conserved between sucrase and isomaltase from different species and several other structurally and functionally related proteins. This is the first report that characterizes a point mutation in the SI gene that is responsible for the Transport incompetence of SI and for its retention between the ER and the Golgi.
Marcus J Propsting - One of the best experts on this subject based on the ideXlab platform.
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a glutamine to proline exchange at amino acid residue 1098 in sucrase causes a temperature sensitive arrest of sucrase isomaltase in the endoplasmic reticulum and cis golgi
Journal of Biological Chemistry, 2003Co-Authors: Marcus J Propsting, Ralf Jacob, Hassan Y. NaimAbstract:A striking feature of phenotype II in congenital sucrase-isomaltase deficiency is the retention of the brush border protein sucrase-isomaltase (SI) in the cis-Golgi. This Transport Block is the consequence of a glutamine to proline substitution at amino acid residue 1098 of the sucrase subunit. Here we provide unequivocal biochemical and confocal data to show that the SI(Q/P) mutant reveals characteristics of a temperature-sensitive mutant. Thus, correct folding, competent intracellular Transport, and full enzymatic activity can be partially restored by expression of the mutant SI(Q/P) at the permissive temperature of 20 degrees C instead of 37 degrees C. The acquisition of normal trafficking and function appears to utilize several cycles of anterograde and retrograde steps between the endoplasmic reticulum and the Golgi implicating the molecular chaperones calnexin and heavy chain-binding protein. The data presented in this communication are to our knowledge the first to implicate a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder.
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a glutamine to proline exchange at amino acid residue 1098 in sucrase causes a temperature sensitive arrest of sucrase isomaltase in the endoplasmic reticulum and cis golgi
Journal of Biological Chemistry, 2003Co-Authors: Marcus J Propsting, Ralf Jacob, Hassan Y. NaimAbstract:Abstract A striking feature of phenotype II in congenital sucrase-isomaltase deficiency is the retention of the brush border protein sucrase-isomaltase (SI) in the cis-Golgi. This Transport Block is the consequence of a glutamine to proline substitution at amino acid residue 1098 of the sucrase subunit. Here we provide unequivocal biochemical and confocal data to show that the SIQ/P mutant reveals characteristics of a temperature-sensitive mutant. Thus, correct folding, competent intracellular Transport, and full enzymatic activity can be partially restored by expression of the mutant SIQ/P at the permissive temperature of 20 °C instead of 37 °C. The acquisition of normal trafficking and function appears to utilize several cycles of anterograde and retrograde steps between the endoplasmic reticulum and the Golgi implicating the molecular chaperones calnexin and heavy chain-binding protein. The data presented in this communication are to our knowledge the first to implicate a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder.
Harry A Quigley - One of the best experts on this subject based on the ideXlab platform.
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the role of aquaporin 4 in optic nerve head astrocytes in experimental glaucoma
PLOS ONE, 2021Co-Authors: Elizabeth C Kimball, Julie Schaub, Sarah Quillen, Casey Keuthan, Mary Ellen Pease, Arina Korneva, Harry A QuigleyAbstract:Purpose To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). Methods C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression, and Transport Block were also analyzed. Results B6 mice had abundant AQP4 expression in Muller cells, astrocytes of retina and myelinated ON (MON), but minimal AQP4in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p = 0.42) and axonal Transport Blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Conclusion Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.
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the role of aquaporin 4 in optic nerve head astrocytes in experimental glaucoma
bioRxiv, 2020Co-Authors: Elizabeth C Kimball, Julie Schaub, Sarah Quillen, Casey Keuthan, Mary Ellen Pease, Arina Korneva, Harry A QuigleyAbstract:Purpose: To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). Methods: C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression & Transport Block was also analyzed. Results: B6 mice presented abundant AQP4 in Muller cells, astrocytes of retina and myelinated ON (MON), but minimal expression in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p=0.42) and axonal Transport Blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Conclusion: Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.
Ralf Jacob - One of the best experts on this subject based on the ideXlab platform.
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a glutamine to proline exchange at amino acid residue 1098 in sucrase causes a temperature sensitive arrest of sucrase isomaltase in the endoplasmic reticulum and cis golgi
Journal of Biological Chemistry, 2003Co-Authors: Marcus J Propsting, Ralf Jacob, Hassan Y. NaimAbstract:A striking feature of phenotype II in congenital sucrase-isomaltase deficiency is the retention of the brush border protein sucrase-isomaltase (SI) in the cis-Golgi. This Transport Block is the consequence of a glutamine to proline substitution at amino acid residue 1098 of the sucrase subunit. Here we provide unequivocal biochemical and confocal data to show that the SI(Q/P) mutant reveals characteristics of a temperature-sensitive mutant. Thus, correct folding, competent intracellular Transport, and full enzymatic activity can be partially restored by expression of the mutant SI(Q/P) at the permissive temperature of 20 degrees C instead of 37 degrees C. The acquisition of normal trafficking and function appears to utilize several cycles of anterograde and retrograde steps between the endoplasmic reticulum and the Golgi implicating the molecular chaperones calnexin and heavy chain-binding protein. The data presented in this communication are to our knowledge the first to implicate a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder.
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a glutamine to proline exchange at amino acid residue 1098 in sucrase causes a temperature sensitive arrest of sucrase isomaltase in the endoplasmic reticulum and cis golgi
Journal of Biological Chemistry, 2003Co-Authors: Marcus J Propsting, Ralf Jacob, Hassan Y. NaimAbstract:Abstract A striking feature of phenotype II in congenital sucrase-isomaltase deficiency is the retention of the brush border protein sucrase-isomaltase (SI) in the cis-Golgi. This Transport Block is the consequence of a glutamine to proline substitution at amino acid residue 1098 of the sucrase subunit. Here we provide unequivocal biochemical and confocal data to show that the SIQ/P mutant reveals characteristics of a temperature-sensitive mutant. Thus, correct folding, competent intracellular Transport, and full enzymatic activity can be partially restored by expression of the mutant SIQ/P at the permissive temperature of 20 °C instead of 37 °C. The acquisition of normal trafficking and function appears to utilize several cycles of anterograde and retrograde steps between the endoplasmic reticulum and the Golgi implicating the molecular chaperones calnexin and heavy chain-binding protein. The data presented in this communication are to our knowledge the first to implicate a temperature-sensitive mutation in an intestinal enzyme deficiency or an intestinal disorder.
Elizabeth C Kimball - One of the best experts on this subject based on the ideXlab platform.
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the role of aquaporin 4 in optic nerve head astrocytes in experimental glaucoma
PLOS ONE, 2021Co-Authors: Elizabeth C Kimball, Julie Schaub, Sarah Quillen, Casey Keuthan, Mary Ellen Pease, Arina Korneva, Harry A QuigleyAbstract:Purpose To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). Methods C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression, and Transport Block were also analyzed. Results B6 mice had abundant AQP4 expression in Muller cells, astrocytes of retina and myelinated ON (MON), but minimal AQP4in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p = 0.42) and axonal Transport Blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Conclusion Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.
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the role of aquaporin 4 in optic nerve head astrocytes in experimental glaucoma
bioRxiv, 2020Co-Authors: Elizabeth C Kimball, Julie Schaub, Sarah Quillen, Casey Keuthan, Mary Ellen Pease, Arina Korneva, Harry A QuigleyAbstract:Purpose: To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). Methods: C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression & Transport Block was also analyzed. Results: B6 mice presented abundant AQP4 in Muller cells, astrocytes of retina and myelinated ON (MON), but minimal expression in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p=0.42) and axonal Transport Blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Conclusion: Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.
