Document Detail

The role of the neutral amino acid transporter SNAT2 in cell volume regulation.
MedLine Citation:
PMID:  16734764     Owner:  NLM     Status:  MEDLINE    
Sodium-dependent neutral amino acid transporter-2 (SNAT2), the ubiquitous member of SLC38 family, accounts for the activity of transport system A for neutral amino acids in most mammalian tissues. As the transport process performed by SNAT2 is highly energized, system A substrates, such as glutamine, glycine, proline and alanine, reach high transmembrane gradients and constitute major components of the intracellular amino acid pool. Moreover, through a complex array of exchange fluxes, involving other amino acid transporters, and of metabolic reactions, such as the synthesis of glutamate from glutamine, SNAT2 activity influences the cell content of most amino acids, thus determining the overall size and the composition of the intracellular amino acid pool. As amino acids represent a large fraction of cell organic osmolytes, changes of SNAT2 activity are followed by modifications in both cell amino acids and cell volume. This mechanism is utilized by many cell types to perform an effective regulatory volume increase (RVI) upon hypertonic exposure. Under these conditions, the expression of SNAT2 gene is induced and newly synthesized SNAT2 proteins are preferentially targeted to the cell membrane, leading to a significant increase of system A transport Vmax. In cultured human fibroblasts incubated under hypertonic conditions, the specific silencing of SNAT2 expression, obtained with anti-SNAT2 siRNAs, prevents the increase in system A transport activity, hinders the expansion of intracellular amino acid pool, and significantly delays cell volume recovery. These results demonstrate the pivotal role played by SNAT2 induction in the short-term hypertonic RVI and suggest that neutral amino acids behave as compatible osmolytes in hypertonically stressed cells.
R Franchi-Gazzola; V Dall'Asta; R Sala; R Visigalli; E Bevilacqua; F Gaccioli; G C Gazzola; O Bussolati
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Acta physiologica (Oxford, England)     Volume:  187     ISSN:  1748-1708     ISO Abbreviation:  Acta Physiol (Oxf)     Publication Date:    2006 May-Jun
Date Detail:
Created Date:  2006-05-31     Completed Date:  2007-01-18     Revised Date:  2009-02-03    
Medline Journal Info:
Nlm Unique ID:  101262545     Medline TA:  Acta Physiol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-83     Citation Subset:  IM    
Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Parma, Italy.
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MeSH Terms
Adaptation, Physiological
Amino Acid Transport System A / physiology*
Amino Acids, Neutral / metabolism*
Biological Transport
Cell Membrane / metabolism
Cell Size
Cells, Cultured
Fibroblasts / metabolism
Gene Expression Regulation
Hypertonic Solutions
RNA Interference
RNA, Small Interfering
Water-Electrolyte Balance
Reg. No./Substance:
0/Amino Acid Transport System A; 0/Amino Acids, Neutral; 0/Hypertonic Solutions; 0/RNA, Small Interfering; 0/SLC38A2 protein, human

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