Regulated exocytosis of an H+/myo-inositol symporter at synapses and growth cones.
Phosphoinositides, synthesized from myo-inositol, play a critical role in the development of growth cones and in synaptic activity. As neurons cannot synthesize inositol, they take it up from the extracellular milieu. Here, we demonstrate that, in brain and PC12 cells, the recently identified H(+)/myo-inositol symporter HMIT is present in intracellular vesicles that are distinct from synaptic and dense-core vesicles. We further show that HMIT can be triggered to appear on the cell surface following cell depolarization, activation of protein kinase C or increased intracellular calcium concentrations. HMIT cell surface expression takes place preferentially in regions of nerve growth and at varicosities and leads to increased myo-inositol uptake. The symporter is then endocytosed in a dynamin-dependent manner and becomes available for a subsequent cycle of stimulated exocytosis. HMIT is thus expressed in a vesicular compartment involved in activity-dependent regulation of myo-inositol uptake in neurons. This may be essential for sustained signaling and vesicular traffic activities in growth cones and at synapses.
Uldry
Marc
M
Institute of Pharmacology and Toxicology, University of Lausanne, Switzerland.
Steiner
Pascal
P
Zurich
Marie-Gabrielle
MG
Béguin
Pascal
P
Hirling
Harald
H
Dolci
Wanda
W
Thorens
Bernard
B
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D051246:Glucose Transport Proteins, Facilitative; D020439:Growth Cones / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013570:Synaptic Membranes / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
D051246:Glucose Transport Proteins, Facilitative; D007295:Inositol Phosphates; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; C486673:Slc2a13 protein, rat