Journal article
MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy
- Abstract:
- MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.2MB, Terms of use)
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(Preview, Supplementary materials, pdf, 25.8MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms12120
Authors
+ British Heart Foundation
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- Funder identifier:
- https://ror.org/02wdwnk04
- Funding agency for:
- Gehmlich, K
- Grant:
- FS/12/40/29712
+ Telethon Foundation
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- Funder identifier:
- https://ror.org/04xraxn18
- Grant:
- GGP12282
+ Agenzia Spaziale Italiana
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- Funder identifier:
- https://ror.org/034zgem50
- Grant:
- 2015-009-R.0
+ Medical Research Council
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- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- G0400153
+ National Institutes of Health
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- Funder identifier:
- https://ror.org/01cwqze88
- Grant:
- HL128457
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 7
- Issue:
- 1
- Article number:
- 12120
- Publication date:
- 2016-06-29
- Acceptance date:
- 2016-05-31
- DOI:
- EISSN:
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2041-1723
- Language:
-
English
- Pubs id:
-
pubs:630613
- UUID:
-
uuid:0242b30c-7bc1-44d2-8dc7-bcea7a2581b4
- Local pid:
-
pubs:630613
- Source identifiers:
-
630613
- Deposit date:
-
2016-06-29
- ARK identifier:
Terms of use
- Copyright holder:
- Lange et al
- Copyright date:
- 2016
- Rights statement:
- © The Author(s) 2016 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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