Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

William C. Wetsel, Ramona M. Rodriguiz, Johann Guillemot, Estelle Rousselet, Rachid Essalmani, Il Hwan Kim, Jesse C. Bryant, Jadwiga Marcinkiewicz, Roxane Desjardins, Robert Day, Daniel B. Constam, Annik Prat, Nabil G. Seidah

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

PC7 belongs to the proprotein convertase family, whose members are implicated in the cleavage of secretory precursors. The in vivo function of PC7 is unknown. Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1 cells coexpressing proBDNF with either PC7 or Furin. Conversely, the processing of proBDNF into BDNF is markedly reduced in the absence of either Furin or PC7 in mouse primary hepatocytes. In vivo we observe that BDNF and PC7 mRNAs are colocalized in mouse hippocampus and amygdala and that mature BDNF protein levels are reduced in these brain areas in PC7 KO mice but not in the hippocampus of PC1/3 KO mice. Various behavioral tests reveal that in PC7 KO mice spatial memory is intact and plasticity of responding is mildly abnormal. Episodic and emotional memories are severely impaired, but both are rescued with the tyrosine receptor kinase B agonist 7,8-dihydroxyflavone. Altogether, these results support an in vivo role for PC7 in the regulation of certain types of cognitive performance, in part via proBDNF processing. Because polymorphic variants of human PC7 are being characterized, it will be important in future studies to determine their effects on additional physiological and behavioral processes.

Original languageEnglish (US)
Pages (from-to)17362-17367
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number43
DOIs
StatePublished - Oct 22 2013

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Brain-Derived Neurotrophic Factor
Learning
Furin
Hippocampus
Proprotein Convertases
Physiological Phenomena
Episodic Memory
COS Cells
Receptor Protein-Tyrosine Kinases
Amygdala
Hepatocytes
proprotein convertase PC7
Messenger RNA
Brain
Proteins

All Science Journal Classification (ASJC) codes

  • General

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Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. / Wetsel, William C.; Rodriguiz, Ramona M.; Guillemot, Johann; Rousselet, Estelle; Essalmani, Rachid; Kim, Il Hwan; Bryant, Jesse C.; Marcinkiewicz, Jadwiga; Desjardins, Roxane; Day, Robert; Constam, Daniel B.; Prat, Annik; Seidah, Nabil G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 43, 22.10.2013, p. 17362-17367.

Research output: Contribution to journalArticle

Wetsel, WC, Rodriguiz, RM, Guillemot, J, Rousselet, E, Essalmani, R, Kim, IH, Bryant, JC, Marcinkiewicz, J, Desjardins, R, Day, R, Constam, DB, Prat, A & Seidah, NG 2013, 'Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 43, pp. 17362-17367. https://doi.org/10.1073/pnas.1314698110
Wetsel, William C. ; Rodriguiz, Ramona M. ; Guillemot, Johann ; Rousselet, Estelle ; Essalmani, Rachid ; Kim, Il Hwan ; Bryant, Jesse C. ; Marcinkiewicz, Jadwiga ; Desjardins, Roxane ; Day, Robert ; Constam, Daniel B. ; Prat, Annik ; Seidah, Nabil G. / Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 43. pp. 17362-17367.
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