Glutamate transporters in bone.
In the central nervous system Na(+)-dependent glutamate transporters bind extracellular glutamate and transport it into cells surrounding the synapse, terminating excitatory signals. These glutamate transporters also function as ion channels. The glutamate transporter, GLAST-1, is expressed in the plasma membrane of osteoblasts and osteocytes and is the same molecular weight as in brain. Thus in bone cells GLAST-1 may transport glutamate or operate as a glutamate gated ion channel. A splice variant, GLAST-1a, is also expressed in bone. Hydropathy and Western blot analysis suggest GLAST-1a adopts a reversed orientation within the cell membrane. Sodium and potassium ion gradients drive glutamate transport but glycosylation, oxidation and phosphorylation modulate transporter activity. Reversal of GLAST-1a would alter these modifications varying its transport activity under the same ionic gradients. The significance of GLAST-1/1a in bone in vivo is unknown. GLAST-1 knockout mice show no major disruption of skeletal development but have not been investigated in detail. Glutamate affects both osteoclast and osteoblast biology and the regulation of GLAST-1 by mechanical loading in bone suggests a role for glutamate transporters in osteogenesis. Differential regulation and modification of GLAST variants may provide an intricate mechanism controlling extracellular glutamate levels and thus its downstream signalling effects in bone.
Mason
D J
DJ
Connective Tissue Biology Laboratories, School of Bioscience, Cardiff University, Cardiff, UK. masondj@cardiff.ac.uk
Huggett
J F
JF