| First Author | Hanics J | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 10 | Pages | E2006-E2015 |
| PubMed ID | 28223495 | Mgi Jnum | J:241650 |
| Mgi Id | MGI:5903335 | Doi | 10.1073/pnas.1700662114 |
| Citation | Hanics J, et al. (2017) Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration. Proc Natl Acad Sci U S A 114(10):E2006-E2015 |
| abstractText | 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. |
