Myo-inositol transporter (SMIT/HMIT)

Myo-inositol transporters, primarily comprising the sodium-coupled myo-inositol transporters (SMIT1/2, encoded by SLC5A3 and SLC5A11) and the proton-coupled myo-inositol transporter (HMIT, encoded by SLC2A13), are integral membrane proteins responsible for maintaining intracellular myo-inositol levels (UniProt P13521, Q96QE3). These transporters play a critical role in osmoregulation, particularly in the kidney and brain, where myo-inositol acts as a compatible osmolyte to protect cells from hypertonic stress (NIH PMC3072476). Beyond osmoregulation, they are essential for providing the substrate for the synthesis of phosphoinositides, which are vital for intracellular signaling pathways (J. Biol. Chem. 277:45219). Dysregulation of these transport processes is implicated in the pathogenesis of diabetic complications, such as neuropathy and nephropathy, where high glucose levels competitively inhibit myo-inositol uptake (PubMed 1641110). Furthermore, the "inositol depletion hypothesis" suggests these transporters are relevant in psychiatric conditions like bipolar disorder, as mood stabilizers like lithium and valproate indirectly influence inositol cycling (Mol. Psychiatry 10:117). In the brain, HMIT is specifically involved in the transport of myo-inositol into neurons and is highly expressed in regions associated with cognitive function (Front. Physiol. 11:609). Targeting these transporters or the pathways they support offers a therapeutic avenue for managing osmotic stress and signaling abnormalities in metabolic and neurological diseases. Current research also explores their role in Down syndrome, where overexpression of SLC5A3 due to gene dosage effects may contribute to cognitive deficits (PubMed 10446060).

Other names

Sodium/myo-inositol cotransporterProton/myo-inositol cotransporterSMITHMITSLC5A3SLC2A13SLC5A11Sodium-coupled myo-inositol transporter 1Sodium-coupled myo-inositol transporter 2Proton-coupled myo-inositol transporter

Modulation of intracellular myo-inositol concentrations through competitive inhibition or indirect depletion of the inositol pool to regulate osmotic balance and phosphoinositide signaling.