G328E和G409E唾液酸转运蛋白错义突变同样损害转运活性，但对运输的影响存在差异。
G328E and G409E sialin missense mutations similarly impair transport activity, but differentially affect trafficking.
作者信息
Myall Nathaniel J, Wreden Christopher C, Wlizla Marcin, Reimer Richard J
机构信息
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Mol Genet Metab. 2007 Dec;92(4):371-4. doi: 10.1016/j.ymgme.2007.08.121. Epub 2007 Oct 22.
Abstract
Two disease-associated missense mutations in the sialin gene (G328E and G409E) have recently been identified in patients with lysosomal free sialic acid storage disease. We have assessed the effect of these mutations and find complete loss of measurable transport activity with both and impaired trafficking of the G409E protein. These results suggest that the two residues are important for proper function of sialin and confirm the association of loss of transport with disease causative mutations.
摘要
最近在溶酶体游离唾液酸贮积症患者中发现了唾液酸蛋白基因的两个疾病相关错义突变（G328E和G409E）。我们评估了这些突变的影响，发现两者均导致可测量的转运活性完全丧失，并且G409E蛋白的运输受损。这些结果表明这两个残基对唾液酸蛋白的正常功能很重要，并证实了转运功能丧失与疾病致病突变之间的关联。
相似文献
1
G328E and G409E sialin missense mutations similarly impair transport activity, but differentially affect trafficking.
Mol Genet Metab. 2007 Dec;92(4):371-4. doi: 10.1016/j.ymgme.2007.08.121. Epub 2007 Oct 22.
2
Molecular pathogenesis of sialic acid storage diseases: insight gained from four missense mutations and a putative polymorphism of human sialin.
Biol Cell. 2008 Sep;100(9):551-9. doi: 10.1042/BC20070166.
3
Varied mechanisms underlie the free sialic acid storage disorders.
J Biol Chem. 2005 Jan 14;280(2):1408-16. doi: 10.1074/jbc.M411295200. Epub 2004 Oct 29.
4
Unraveling the molecular pathogenesis of free sialic acid storage disorders: altered targeting of mutant sialin.
Mol Genet Metab. 2002 Sep-Oct;77(1-2):99-107. doi: 10.1016/s1096-7192(02)00124-5.
5
Functional characterization of vesicular excitatory amino acid transport by human sialin.
J Neurochem. 2011 Oct;119(1):1-5. doi: 10.1111/j.1471-4159.2011.07388.x. Epub 2011 Aug 22.
6
The molecular mechanism of sialic acid transport mediated by Sialin.
Sci Adv. 2023 Jan 20;9(3):eade8346. doi: 10.1126/sciadv.ade8346.
7
Functional characterization of wild-type and mutant human sialin.
EMBO J. 2004 Nov 24;23(23):4560-70. doi: 10.1038/sj.emboj.7600464. Epub 2004 Oct 28.
8
Sialic acid storage disease and related disorders.
Genet Test. 2003 Summer;7(2):113-21. doi: 10.1089/109065703322146795.
9
Salla disease and ISSD--what does the future hold?
Mol Genet Metab. 2004 Jun;82(2):99-100. doi: 10.1016/j.ymgme.2004.04.002.
10
Biochemical and molecular analyses of infantile free sialic acid storage disease in North American children.
Am J Med Genet A. 2003 Jul 1;120A(1):28-33. doi: 10.1002/ajmg.a.20024.
引用本文的文献
1
The molecular mechanism of sialic acid transport mediated by Sialin.
Sci Adv. 2023 Jan 20;9(3):eade8346. doi: 10.1126/sciadv.ade8346.
2
Free sialic acid storage disorder: Progress and promise.
Neurosci Lett. 2021 Jun 11;755:135896. doi: 10.1016/j.neulet.2021.135896. Epub 2021 Apr 20.
3
Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?
Front Cell Neurosci. 2013 Aug 30;7:139. doi: 10.3389/fncel.2013.00139.
4
Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a Common Novel SLC17A5 Mutation.
JIMD Rep. 2014;12:79-84. doi: 10.1007/8904_2013_247. Epub 2013 Jul 31.
5
Synapse location during growth depends on glia location.
Cell. 2013 Jul 18;154(2):337-50. doi: 10.1016/j.cell.2013.06.028.
6
Structure-function studies of the SLC17 transporter sialin identify crucial residues and substrate-induced conformational changes.
J Biol Chem. 2010 Jun 18;285(25):19316-23. doi: 10.1074/jbc.M110.130716. Epub 2010 Apr 27.
7
The lysosomal sialic acid transporter sialin is required for normal CNS myelination.
J Neurosci. 2009 Dec 9;29(49):15355-65. doi: 10.1523/JNEUROSCI.3005-09.2009.
本文引用的文献
1
Membrane topology of the Drosophila vesicular glutamate transporter.
J Neurochem. 2007 Jun;101(6):1662-71. doi: 10.1111/j.1471-4159.2007.04518.x. Epub 2007 Mar 29.
2
Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter.
Nature. 2007 Jan 25;445(7126):387-93. doi: 10.1038/nature05455. Epub 2007 Jan 17.
3
Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters.
Nature. 2005 Sep 8;437(7056):215-23. doi: 10.1038/nature03978. Epub 2005 Jul 24.
4
Varied mechanisms underlie the free sialic acid storage disorders.
J Biol Chem. 2005 Jan 14;280(2):1408-16. doi: 10.1074/jbc.M411295200. Epub 2004 Oct 29.
5
Functional characterization of wild-type and mutant human sialin.
EMBO J. 2004 Nov 24;23(23):4560-70. doi: 10.1038/sj.emboj.7600464. Epub 2004 Oct 28.
6
A novel mutation in the SLC17A5 gene causing both severe and mild phenotypes of free sialic acid storage disease in one inbred Bedouin kindred.
Mol Genet Metab. 2004 Jun;82(2):167-72. doi: 10.1016/j.ymgme.2004.03.005.
7
Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity.
Mol Genet Metab. 2004 Jun;82(2):137-43. doi: 10.1016/j.ymgme.2004.03.001.
8
Sialin expression in the CNS implicates extralysosomal function in neurons.
Neurobiol Dis. 2004 Mar;15(2):251-61. doi: 10.1016/j.nbd.2003.11.017.
9
The H+-coupled electrogenic lysosomal amino acid transporter LYAAT1 localizes to the axon and plasma membrane of hippocampal neurons.
J Neurosci. 2003 Feb 15;23(4):1265-75. doi: 10.1523/JNEUROSCI.23-04-01265.2003.
10
Unraveling the molecular pathogenesis of free sialic acid storage disorders: altered targeting of mutant sialin.
Mol Genet Metab. 2002 Sep-Oct;77(1-2):99-107. doi: 10.1016/s1096-7192(02)00124-5.
Zotero 插件