PMID- 26431040
OWN - NLM
STAT- MEDLINE
DCOM- 20160608
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 10
DP  - 2015
TI  - Physiological Roles of Calpain 1 Associated to Multiprotein NMDA Receptor 
      Complex.
PG  - e0139750
LID - 10.1371/journal.pone.0139750 [doi]
LID - e0139750
AB  - We have recently demonstrated that in resting conditions calpain 1, but not 
      calpain 2, is specifically associated to the N-Methyl-D-Aspartate receptor 
      (NMDAR) multiprotein complex. We are here reporting that in SKNBE neuroblastoma 
      cells or in freshly isolated nerve terminals from adult rat hippocampus, the 
      proteolytic activity of calpain 1 resident at the NMDAR is very low under basal 
      conditions and greatly increases following NMDAR stimulation. Since the protease 
      resides at the NMDAR in saturating amounts, variations in Ca2+ influx promote an 
      increase in calpain 1 activity without affecting the amount of the protease 
      originally associated to NMDAR. In all the conditions examined, resident calpain 
      1 specifically cleaves NR2B at the C-terminal region, leading to its 
      internalization together with NR1 subunit. While in basal conditions 
      intracellular membranes include small amounts of NMDAR containing the 
      calpain-digested NR2B, upon NMDAR stimulation nearly all the receptor molecules 
      are internalized. We here propose that resident calpain 1 is involved in NMDAR 
      turnover, and following an increase in Ca2+ influx, the activated protease, by 
      promoting the removal of NMDAR from the plasma membranes, can decrease Ca2+ 
      entrance through this channel. Due to the absence of calpastatin in such cluster, 
      the activity of resident calpain 1 may be under the control of HSP90, whose 
      levels are directly related to the activation of this protease. Observations of 
      different HSP90/calpain 1 ratios in different ultrasynaptic compartments support 
      this conclusion.
FAU - Averna, Monica
AU  - Averna M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy; Center of Excellence for 
      Biomedical Research (CEBR), University of Genova, Viale Benedetto XV, 1-16132, 
      Genova, Italy.
FAU - Pellegrini, Matteo
AU  - Pellegrini M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy.
FAU - Cervetto, Chiara
AU  - Cervetto C
AD  - Department of Pharmacy, Pharmacology and Toxicology Section, University of 
      Genova, Viale Cembrano 4, 16148, Genova, Italy.
FAU - Pedrazzi, Marco
AU  - Pedrazzi M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy.
FAU - Bavestrello, Margherita
AU  - Bavestrello M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy.
FAU - De Tullio, Roberta
AU  - De Tullio R
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy; Center of Excellence for 
      Biomedical Research (CEBR), University of Genova, Viale Benedetto XV, 1-16132, 
      Genova, Italy.
FAU - Salamino, Franca
AU  - Salamino F
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy; Center of Excellence for 
      Biomedical Research (CEBR), University of Genova, Viale Benedetto XV, 1-16132, 
      Genova, Italy.
FAU - Pontremoli, Sandro
AU  - Pontremoli S
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy.
FAU - Melloni, Edon
AU  - Melloni E
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, University of 
      Genova, Viale Benedetto XV, 1-16132, Genova, Italy; Center of Excellence for 
      Biomedical Research (CEBR), University of Genova, Viale Benedetto XV, 1-16132, 
      Genova, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151002
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 3.4.22.- (Calpain)
SB  - IM
MH  - Animals
MH  - Calpain/*physiology
MH  - HSP90 Heat-Shock Proteins/physiology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
PMC - PMC4592069
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/10/03 06:00
MHDA- 2016/06/09 06:00
PMCR- 2015/10/02
CRDT- 2015/10/03 06:00
PHST- 2015/05/14 00:00 [received]
PHST- 2015/09/15 00:00 [accepted]
PHST- 2015/10/03 06:00 [entrez]
PHST- 2015/10/03 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
PHST- 2015/10/02 00:00 [pmc-release]
AID - PONE-D-15-21009 [pii]
AID - 10.1371/journal.pone.0139750 [doi]
PST - epublish
SO  - PLoS One. 2015 Oct 2;10(10):e0139750. doi: 10.1371/journal.pone.0139750. 
      eCollection 2015.