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

Publication ,  Journal Article
Wetsel, WC; Rodriguiz, RM; Guillemot, J; Rousselet, E; Essalmani, R; Kim, IH; Bryant, JC; Marcinkiewicz, J; Desjardins, R; Day, R; Constam, DB ...
Published in: Proc Natl Acad Sci U S A
October 22, 2013

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

October 22, 2013

Volume

110

Issue

43

Start / End Page

17362 / 17367

Location

United States

Related Subject Headings

  • Subtilisins
  • RNA, Messenger
  • Protein Precursors
  • Mice, Knockout
  • Mice
  • Memory
  • Maze Learning
  • Male
  • In Situ Hybridization
  • Humans
 

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Wetsel, W. C., Rodriguiz, R. M., Guillemot, J., Rousselet, E., Essalmani, R., Kim, I. H., … Seidah, N. G. (2013). Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. Proc Natl Acad Sci U S A, 110(43), 17362–17367. https://doi.org/10.1073/pnas.1314698110
Wetsel, William C., Ramona M. Rodriguiz, Johann Guillemot, Estelle Rousselet, Rachid Essalmani, Il Hwan Kim, Jesse C. Bryant, et al. “Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice.Proc Natl Acad Sci U S A 110, no. 43 (October 22, 2013): 17362–67. https://doi.org/10.1073/pnas.1314698110.
Wetsel WC, Rodriguiz RM, Guillemot J, Rousselet E, Essalmani R, Kim IH, et al. Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17362–7.
Wetsel, William C., et al. “Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice.Proc Natl Acad Sci U S A, vol. 110, no. 43, Oct. 2013, pp. 17362–67. Pubmed, doi:10.1073/pnas.1314698110.
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. Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17362–17367.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

October 22, 2013

Volume

110

Issue

43

Start / End Page

17362 / 17367

Location

United States

Related Subject Headings

  • Subtilisins
  • RNA, Messenger
  • Protein Precursors
  • Mice, Knockout
  • Mice
  • Memory
  • Maze Learning
  • Male
  • In Situ Hybridization
  • Humans