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The Journal of Neuroscience, February 15, 2003, 23(4):1265
The H+-Coupled Electrogenic Lysosomal Amino Acid
Transporter LYAAT1 Localizes to the Axon and Plasma Membrane of
Hippocampal Neurons
Christopher C.
Wreden1,
Juliette
Johnson2,
Cindy
Tran1,
Rebecca P.
Seal1,
David R.
Copenhagen2,
Richard J.
Reimer1, 3, and
Robert H.
Edwards1
Departments of 1 Neurology and Physiology and
2 Ophthalmology and Physiology, and 3 Graduate
Programs in Neuroscience and Cell Biology, University of California San
Francisco School of Medicine, San Francisco, California 94143
Recent work has identified a lysosomal protein that transports
neutral amino acids (LYAAT1). We now show that LYAAT1 mediates H+ cotransport with a stoichiometry of 1 H+/1 amino acid, consistent with a role in the
active efflux of amino acids from lysosomes. In neurons, however,
LYAAT1 localizes to axonal processes as well as lysosomes. In axons
LYAAT1 fails to colocalize with synaptic markers. Rather, axonal LYAAT1
colocalizes with the exocyst, suggesting a role for membranes
expressing LYAAT1 in specifying sites for exocytosis. A protease
protection assay and measurements of intracellular pH further indicate
abundant expression at the plasma membrane, raising the possibility of physiological roles for LYAAT1 on the cell surface as well as in lysosomes.
Key words:
LYAAT1; lysosome; neutral amino acid transport; exocyst; axon; neuronal ceroid lipofuscinosis
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341265-11$05.00/0
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