The glutamate transporter GLAST-1 (EAAT-1) is expressed in the plasma membrane of osteocytes and is responsive to extracellular glutamate concentration.

Abstract:

:The glutamate/aspartate transporter GLAST-1 is expressed in bone in vivo and also exists as a splice variant (GLAST-1a) in which exon 3 is excluded. Since GLAST-1 expression is regulated in bone in response to osteogenic mechanical stimuli in vivo and binding of glutamate to receptors on osteoblasts increases osteoblast number and activity in vitro, control of extracellular glutamate concentrations may be critical for balanced bone remodelling. To determine whether GLAST isoforms may act to regulate extracellular glutamate concentration in bone we investigated whether their pattern or level of expression is responsive to glutamate concentration in bone cells. GLAST-1a mRNA is expressed at lower levels than GLAST-1 mRNA in all cells examined. The GLAST-1a/GLAST-1 mRNA ratio is greater in MLO-Y4 osteocytes than in SaOS-2 osteoblast-like cells, although this does vary in SaOS-2 cells in response to extracellular glutamate concentration. Transfection of MLO-Y4 cells with green fluorescent protein (GFP)-tagged GLAST isoforms revealed a plasma membrane localization of GLAST-1, consistent with its transporter function, whereas GLAST-1a appeared to be expressed within internal vesicles. Interestingly, low extracellular glutamate concentrations redistributed GLAST-1-GFP into a similar internal expression pattern. Regulation of the expression and distribution of GLAST-1 by extracellular glutamate in bone cells indicates that it may regulate glutamate signalling in bone, consistent with its operation in the central nervous system.

journal_name

Biochem Soc Trans

authors

Huggett JF,Mustafa A,O'neal L,Mason DJ

doi

10.1042/bst0300890

keywords:

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

890-3

issue

Pt 6

eissn

0300-5127

issn

1470-8752

journal_volume

30

pub_type

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