DMT1 as a Candidate for Non-Transferrin-Bound Iron Uptake in the Peripheral Nervous System

MARTINEZ VIVOT, ROCÍO; GOITIA, BELÉN; USACH, VANINA; SETTON - AVRUJ, PATRICIA

BIOFACTORS

IOS PRESS

Lugar: Amsterdam; Año: 2013

0951-6433

Iron, either in its free form or as holotransferrin (hTf), prevents the dedifferentiation of Schwann cells (SC), cells responsible for the myelination of the peripheral nervous system (PNS). This dedifferentiation is promoted by serum deprivation through cAMP release, PKA activation and CREB phosphorylation (1). Since iron elicits its effect in a transferrin (Tf)-free environment, in the present work we postulate that there must be a non-transferrin-bound iron (NTBI) uptake involved. Divalent metal transporter 1(DMT1) has been widely described in literature as an iron metabolism key player, but never before in the peripheral nervous system (PNS) context. The presence of DMT1 was demonstrated in nerve homogenate, isolated adult-rat myelin and cultured SC by Western Blot (WB) analysis and confirmed through its co-localization with S-100β (SC marker) by immunocytochemical and immunohistochemical analyses. Furthermore, the existence of its mRNA was verified by RT-PCR in sciatic nerve homogenate and along the SC progeny. Finally we describe DMT1’s subcelullar location in the plasma membrane by confocal microscopy of SC and WB of different subcellular fractions. These data allow us to confirm the existence of DMT1 as part of a Tf independent iron uptake mechanism in SC and lead us to postulate a crucial role for iron in SC maturation and, as a consequence, in PNS myelination