pH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1/2 pathway

Abstract

<jats:title>Abstract</jats:title><jats:p>We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pH<jats:sub>i</jats:sub>). We show that OPC differentiation is dependent primarily on a permissive pH<jats:sub>i</jats:sub> value. The highest differentiation levels were observed for pH<jats:sub>i</jats:sub> values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pH<jats:sub>i</jats:sub> of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pH<jats:sub>i</jats:sub> shift. These results indicate that pH<jats:sub>i</jats:sub>, acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pH<jats:sub>i</jats:sub> pathway is involved in the process of retinoic acid‐induced OPC differentiation. © 2006 Wiley‐Liss, Inc.</jats:p>

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