| First Author | Neverisky DL | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 7 | Pages | 2828-2838 |
| PubMed ID | 28283543 | Mgi Jnum | J:252684 |
| Mgi Id | MGI:5927247 | Doi | 10.1096/fj.201601334R |
| Citation | Neverisky DL, et al. (2017) KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk. FASEB J 31(7):2828-2838 |
| abstractText | Voltage-gated potassium channels formed by KCNQ2 and KCNQ3 are essential for normal neuronal excitability. KCNQ2/3 channel activity is augmented in vivo by phosphatidylinositol 4,5-bisphosphate (PIP2), which is generated from myo-inositol, an osmolyte transported into cells by sodium-dependent myo-inositol transporters (SMITs). Here, we discovered that KCNQ2/3 channels isoform-specifically colocalize with SMIT1 and SMIT2 at sciatic nerve nodes of Ranvier and in axon initial segments, and form channel-transporter complexes in vitro and in vivo KCNQ2/3 coexpression protected SMIT1 activity from the otherwise inhibitory effects of cellular depolarization imposed by elevating extracellular [K+], and KCNQ2 was required for potentiation of SMIT activity by myo-inositol preincubation. Cytoskeletal disruption, which speeds PIP2 dispersion, attenuated potentiation of KCNQ2/3 currents by SMIT1-mediated myo-inositol uptake, suggesting close channel-transporter juxtaposition ensures KCNQ2/3 exposure to locally high myo-inositol-derived PIP2 concentrations. Thus, KCNQ2/3-SMIT1/2 coassembly permits cross talk via physical interaction, and may also be required for optimal, reciprocal indirect regulation via membrane potential and PIP2, especially within the specialized architecture of axons.-Neverisky, D. L., Abbott, G. W. KCNQ-SMIT complex formation facilitates ion channel-solute transporter cross talk. |
