Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration

János Hanics, Edit Szodorai, Giuseppe Tortoriello, Katarzyna Malenczyk, Erik Keimpema, Gert Lubec, Zsófia Hevesi, Mirjam I. Lutz, Márk Kozsurek, Zita Puskár, Zsuzsanna E. Tóth, Ludwig Wagner, Gábor G. Kovács, Tomas G M Hökfelt, Tibor Harkany, Alán Alpár

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10 Citations (Scopus)

Abstract

The rostral migratory stream (RMS) is viewed as a glia-enriched conduit of forward-migrating neuroblasts in which chemorepulsive signals control the pace of forward migration. Here we demonstrate the existence of a scaffold of neurons that receive synaptic inputs within the rat, mouse, and human fetal RMS equivalents. These neurons express secretagogin, a Ca2+-sensor protein, to execute an annexin V-dependent externalization of matrix metalloprotease-2 (MMP-2) for reconfiguring the extracellular matrix locally. Mouse genetics combined with pharmacological probing in vivo and in vitro demonstrate that MMP-2 externalization occurs on demand and that its loss slows neuroblast migration. Loss of function is particularly remarkable upon injury to the olfactory bulb. Cumulatively, we identify a signaling cascade that provokes structural remodeling of the RMS through recruitment of MMP-2 by a previously unrecognized neuronal constituent. Given the life-long presence of secretagogin-containing neurons in human, this mechanism might be exploited for therapeutic benefit in rescue strategies.

Original languageEnglish
Pages (from-to)E2006-E2015
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number10
DOIs
Publication statusPublished - Mar 7 2017

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Keywords

  • Calcium-binding protein
  • Cell motility
  • Human fetus
  • Olfactory system
  • Restorative strategy

ASJC Scopus subject areas

  • General

Cite this

Hanics, J., Szodorai, E., Tortoriello, G., Malenczyk, K., Keimpema, E., Lubec, G., Hevesi, Z., Lutz, M. I., Kozsurek, M., Puskár, Z., Tóth, Z. E., Wagner, L., Kovács, G. G., Hökfelt, T. G. M., Harkany, T., & Alpár, A. (2017). Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration. Proceedings of the National Academy of Sciences of the United States of America, 114(10), E2006-E2015. https://doi.org/10.1073/pnas.1700662114