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

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

Proceedings of the National Academy of Sciences - PNAS, 2017-03, Vol.114 (10), p.E2006-E2015 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration
Autor: Hanics, János ; Szodorai, Edit ; Tortoriello, Giuseppe ; Malenczyk, Katarzyna ; Keimpema, Erik ; Lubec, Gert ; Hevesi, Zsófia ; Lutz, Mirjam I. ; Kozsurek, Márk ; Puskár, Zita ; Tóth, Zsuzsanna E. ; Wagner, Ludwig ; Kovács, Gábor G. ; Hökfelt, Tomas G. M. ; Harkany, Tibor ; Alpár, Alán
Assuntos: Animals ; Annexin A5 - genetics ; Annexin A5 - metabolism ; Biological Sciences ; Calcium ; Calcium - metabolism ; Cell Movement ; Fetus ; Gene Expression Regulation ; Humans ; Male ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; Medicin och hälsovetenskap ; Mice ; Microtomy ; Neuroglia - metabolism ; Neuroglia - ultrastructure ; Neurons ; Neurons - metabolism ; Neurons - ultrastructure ; Olfactory Bulb - cytology ; Olfactory Bulb - metabolism ; PNAS Plus ; Primary Cell Culture ; Proteins ; Rats ; Rats, Wistar ; Rodents ; Secretagogins - genetics ; Secretagogins - metabolism ; Synapses - metabolism ; Synapses - ultrastructure ; Tissue Culture Techniques
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2017-03, Vol.114 (10), p.E2006-E2015
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Contributed by Tomas G. M. Hökfelt, January 19, 2017 (sent for review September 15, 2016; reviewed by Leszek Kaczmarek, George Kuhn, and Armen Saghatelyan)
Author contributions: J.H., E.S., T.G.M.H., T.H., and A.A. designed research; J.H., E.S., Z.H., M.L., M.K., Z.P., Z.E.T., and A.A. performed research; L.W. and G.G.K. contributed new reagents/analytic tools; J.H., E.S., G.T., K.M., E.K., G.L., T.H., and A.A. analyzed data; and T.H. and A.A. wrote the paper.
1J.H. and E.S. contributed equally to this work.
Reviewers: L.K., Nencki Institute; G.K., University of Gothenburg; and A.S., Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec.
2Present address: Thermo Fisher Scientific, Life Sciences Solutions Group, 20900 Monza, Italy.
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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

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

United States: National Academy of Sciences

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