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Article

  • The EMBO Journal (2004) 23, 531 - 540
  • doi:10.1038/sj.emboj.7600072

Published online: 29 January 2004

Regulated exocytosis of an H+/myo-inositol symporter at synapses and growth cones

Marc Uldry1, Pascal Steiner2, Marie-Gabrielle Zurich3, Pascal Béguin1, Harald Hirling2, Wanda Dolci1 and Bernard Thorens1,3

  1. Institute of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland
  2. Faculte des Sciences de la Vie, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
  3. Institute of Physiology, University of Lausanne, Lausanne, Switzerland

Correspondence to:

Bernard Thorens, Institute of Pharmacology and Toxicology, University of Lausanne, 27 rue du Bugnon, CH-1005 Lausanne, Switzerland. Tel.: +41 21 692 5390; Fax: +41 21 692 5355; E-mail: bernard.thorens@ipharm.unil.ch

Received 21 July 2003; Accepted 16 December 2003

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.

  • Keywords:

    • growth cones,
    • myo-inositol,
    • neurons,
    • SLC2A13,
    • synapses,
    • transporter