Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asymmetrical distribution of Na(+)- and Cl(-)-dependent neurotransmitter transporters on the cell surface of polarized cells seems to be a generalized feature in this gene family. In the present study we analyzed the subcellular distribution of the various isoforms of the glycine transporters GLYT1 and GLYT2 after heterologous expression in polarized MDCK cells and in hippocampal neurons. Our results indicate that glycine transporters are asymmetrically distributed in an isoform- and cell-type-specific manner. GLYT1b is localized in the basolateral and somatodendritic domains of MDCK cells and neurons, respectively. However, GLYT1a is somatodendritic in neurons but is predominantly expressed in the apical surface of MDCK cells. The two isoforms of GLYT2 (GLYT2a and GLYT2b) are found at the apical surface in epithelial cells but are uniformly distributed in neurons. By using site-directed mutagenesis we have been able to identify signals for basolateral/somatodendritic localization in the amino-terminal region of GLYT1 and in two dileucine motifs located in the carboxyl tail of this protein. These results contribute to defining the mechanisms of asymmetrical distribution of transporters on the cell surface of polarized cells.
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PMID:Polarized distribution of glycine transporter isoforms in epithelial and neuronal cells. 1066 9

The asymmetrical distribution of neurotransmitter transporters on the cell surface of neurons seems to be a generalized feature of these proteins, and is thought to be important for an appropriate removal of neurotransmitters from the extracellular milieu. To study the subcellular distribution of the glycine transporter isoforms (GLYT1a, GLYT1b, GLYT2a and GLYT2b), these proteins were expressed in epithelial cells [Madin-Darby canine kidney (MDCK) cells] and in cultured hippocampal neurons, as models of polarized cells. The localization of the transporters was assessed by immunofluorescence assays. Our results indicated that the subcellular distribution of glycine transporters is dependent on both the protein isoform and the cell type. By using site-directed mutagenesis we have been able to identify signals for basolateral/somatodendritic localization in the alternative amino terminal region of GLYT1 and in two di-leucine motifs that are located in the carboxyl tail of this protein. Moreover, the N-glycosylation sites located in the large extracellular loop of GLYT2 are involved in apical localization of this protein in polarized MDCK cells. These results contribute to define the mechanisms of asymmetrical distribution of transporters on the cell surface of polarized cells.
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PMID:Molecular determinants involved in the asymmetrical distribution of glycine transporters in polarized cells. 1170 68