PMID- 25575026
OWN - NLM
STAT- MEDLINE
DCOM- 20151229
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 1
DP  - 2015
TI  - Interaction between calpain-1 and HSP90: new insights into the regulation of 
      localization and activity of the protease.
PG  - e0116738
LID - 10.1371/journal.pone.0116738 [doi]
LID - e0116738
AB  - Here we demonstrate that heat shock protein 90 (HSP90) interacts with calpain-1, 
      but not with calpain-2, and forms a discrete complex in which the protease 
      maintains its catalytic activity, although with a lower affinity for Ca2+. 
      Equilibrium gel distribution experiments show that this complex is composed by an 
      equal number of molecules of each protein partner. Moreover, in resting cells, 
      cytosolic calpain-1 is completely associated with HSP90. Since calpain-1, in 
      association with HSP90, retains its proteolytic activity, and the chaperone is 
      displaced by calpastatin also in the absence of Ca2+, the catalytic cleft of the 
      protease is not involved in this association. Thus, calpain-1 can form two 
      distinct complexes depending on the availability of calpastatin in the cytosol. 
      The occurrence of a complex between HSP90 and calpain-1, in which the protease is 
      still activable, can prevent the complete inhibition of the protease even in the 
      presence of high calpastatin levels. We also demonstrate that in basal cell 
      conditions HSP90 and calpain-1, but not calpain-2, are inserted in the 
      multi-protein N-Methyl-D-Aspartate receptor (NMDAR) complex. The amount of 
      calpain-1 at the NMDAR cluster is not modified in conditions of increased 
      [Ca2+]i, and this resident protease is involved in the processing of NMDAR 
      components. Finally, the amount of calpain-1 associated with NMDAR cluster is 
      independent from Ca2+-mediated translocation. Our findings show that HSP90 plays 
      an important role in maintaining a given and proper amount of calpain-1 at the 
      functional sites.
FAU - Averna, Monica
AU  - Averna M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - De Tullio, Roberta
AU  - De Tullio R
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - Pedrazzi, Marco
AU  - Pedrazzi M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - Bavestrello, Margherita
AU  - Bavestrello M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - Pellegrini, Matteo
AU  - Pellegrini M
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - Salamino, Franca
AU  - Salamino F
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - Pontremoli, Sandro
AU  - Pontremoli S
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
FAU - Melloni, Edon
AU  - Melloni E
AD  - Department of Experimental Medicine (DIMES)-Biochemistry Section, and Center of 
      Excellence for Biomedical Research (CEBR), University of Genoa, Viale Benedetto 
      XV, 1-16132 Genoa, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150109
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Ions)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Recombinant Proteins)
RN  - 79079-11-1 (calpastatin)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.22.- (Calpain)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/chemistry/metabolism
MH  - Calcium-Binding Proteins/chemistry/genetics/metabolism
MH  - Calpain/chemistry/*metabolism
MH  - Cell Line
MH  - HSP90 Heat-Shock Proteins/chemistry/genetics/*metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Ions/chemistry
MH  - Male
MH  - Mice
MH  - Microscopy, Confocal
MH  - Peptide Hydrolases/metabolism
MH  - Protein Binding
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/chemistry/metabolism
MH  - Recombinant Proteins/biosynthesis/chemistry/genetics
PMC - PMC4289065
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/01/13 06:00
MHDA- 2015/12/30 06:00
PMCR- 2015/01/09
CRDT- 2015/01/10 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2014/12/12 00:00 [accepted]
PHST- 2015/01/10 06:00 [entrez]
PHST- 2015/01/13 06:00 [pubmed]
PHST- 2015/12/30 06:00 [medline]
PHST- 2015/01/09 00:00 [pmc-release]
AID - PONE-D-14-34589 [pii]
AID - 10.1371/journal.pone.0116738 [doi]
PST - epublish
SO  - PLoS One. 2015 Jan 9;10(1):e0116738. doi: 10.1371/journal.pone.0116738. 
      eCollection 2015.