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

Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E2006-E2015. doi: 10.1073/pnas.1700662114. Epub 2017 Feb 21.


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.

Keywords: calcium-binding protein; cell motility; human fetus; olfactory system; restorative strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / genetics
  • Annexin A5 / metabolism
  • Calcium / metabolism*
  • Cell Movement
  • Fetus
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Microtomy
  • Neuroglia / metabolism*
  • Neuroglia / ultrastructure
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism*
  • Primary Cell Culture
  • Rats
  • Rats, Wistar
  • Secretagogins / genetics*
  • Secretagogins / metabolism
  • Synapses / metabolism
  • Synapses / ultrastructure
  • Tissue Culture Techniques


  • Annexin A5
  • Secretagogins
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Calcium