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pERK1/2 Peripheral Recruitment and Filopodia Protrusion Augment Oligodendrocyte Progenitor Cell Migration: Combined Effects of PDGF-A and Fibronectin

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Abstract

Oligodendrocyte progenitor cell (OPC) migration is critical for effective myelination of the central nervous system. Not only during normal myelination but also during remyelination, the growth factors (GFs) and extracellular matrix (ECM) protein affect the OPC migration. Studies showed the altered levels of GFs and ECM in the demyelinating lesions. In our earlier studies, we have shown that the effect of platelet-derived growth factor alpha (PDGF-A) on OPC migration is dose- and time-dependent. In that we have shown that the physiological concentration (1 ng/ml) of PDGF-A was unable to induce OPC migration at transient exposure (30 min). However, the involvement of ECM in the regulation of PDGF-A mediated OPC migration was not clear. In the present study, we have used fibronectin (FN) as ECM. PDGF-A and FN have similar and overlapping intracellular signaling pathways including the extracellular regulated kinases 1 and 2 (ERK1/2). Here we demonstrate how physiological concentration of PDGF-A combines with FN to augment OPC migration in vitro. The present study is first of its kind to show the importance of the synergistic effects of PDGF-A and FN on peripheral recruitment of phosphorylated/activated ERK1/2 (pERK1/2), actin-pERK1/2 co-localization, and filopodia formation, which are essential for the enhanced OPC migration. These findings were further confirmed by ERK1/2 inhibition studies, using the pharmacological inhibitor U0126. An understanding of these complex interactions may lead to additional strategies for transplanting genetically modified OPCs to repair widespread demyelinated lesions.

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Acknowledgments

This work was funded by a grant from Science and Engineering Research Board (SERB) (No.-SR/FT/LS-52/2011, 1st May, 2012), New Delhi, India. We also thank DBT-MSUB-ILSPARE and SERB, India, for awarding JRFs to AT and ZSP, respectively. We are highly thankful to DBT-MSUB-ILSPARE programme for the confocal microscopy facility at Dr. Vikram Sarabhai Science Block, Faculty of Science, MSU, Vadodara.

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    1. Division of Neurobiology, Department of Zoology, Faculty of Science, The M. S. University of Baroda, Vadodara, Gujarat, 390 002, India

      Ashutosh Tripathi, Zalak S. Parikh & Prakash P. Pillai

    2. Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, Canada

      Parvez Vora

    3. University of Manitoba, Winnipeg, MB, Canada

      Emma E. Frost

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    Ashutosh Tripathi and Zalak S. Parikh have contributed equally to this work.

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    Tripathi, A., Parikh, Z.S., Vora, P. et al. pERK1/2 Peripheral Recruitment and Filopodia Protrusion Augment Oligodendrocyte Progenitor Cell Migration: Combined Effects of PDGF-A and Fibronectin. Cell Mol Neurobiol 37, 183–194 (2017). https://doi.org/10.1007/s10571-016-0359-y

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