title: Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration.
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.
authors.affiliation: MTA-SE NAP B Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, H-1051 Budapest, Hungary.|Department of Anatomy, Histology, and Embryology, Semmelweis University, H-1085 Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Hanics
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.|Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Edit
authors.initials: E
authors.lastname: Szodorai
authors.affiliation: Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tortoriello
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.|Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Malenczyk
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Erik
authors.initials: E
authors.lastname: Keimpema
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.affiliation: MTA-SE NAP B Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, H-1051 Budapest, Hungary.|Department of Anatomy, Histology, and Embryology, Semmelweis University, H-1085 Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Hevesi
authors.affiliation: Institute of Neurology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Mirjam I
authors.initials: MI
authors.lastname: Lutz
authors.affiliation: Department of Anatomy, Histology, and Embryology, Semmelweis University, H-1085 Budapest, Hungary.
authors.forename: Márk
authors.initials: M
authors.lastname: Kozsurek
authors.affiliation: Department of Anatomy, Histology, and Embryology, Semmelweis University, H-1085 Budapest, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Puskár
authors.affiliation: Department of Anatomy, Histology, and Embryology, Semmelweis University, H-1085 Budapest, Hungary.
authors.forename: Zsuzsanna E
authors.initials: ZE
authors.lastname: Tóth
authors.affiliation: Department of Internal Medicine III, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wagner
authors.affiliation: Institute of Neurology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.affiliation: Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden, tomas.hokfelt@ki.se alpar.alan@med.semmelweis-univ.hu.
authors.forename: Tomas G M
authors.initials: TG
authors.lastname: Hökfelt
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.|Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
authors.affiliation: MTA-SE NAP B Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Academy of Sciences, H-1051 Budapest, Hungary; tomas.hokfelt@ki.se alpar.alan@med.semmelweis-univ.hu.|Department of Anatomy, Histology, and Embryology, Semmelweis University, H-1085 Budapest, Hungary.
authors.forename: Alán
authors.initials: A
authors.lastname: Alpár
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement; D005333:Fetus; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008867:Microtomy; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D064046:Secretagogins / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D046509:Tissue Culture Techniques
chemical_list: D017304:Annexin A5; D064046:Secretagogins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D002118:Calcium
keywords: calcium-binding protein; cell motility; human fetus; olfactory system; restorative strategy