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The cardiac syndecan-4 interactome reveals a role for syndecan-4 in nuclear translocation of muscle LIM protein (MLP)
| Content Provider | Scilit |
|---|---|
| Author | Mathiesen, Sabrina Bech Lunde, Marianne Aronsen, Jan Magnus Romaine, Andreas Kaupang, Anita Martinsen, Marita de Souza, Gustavo Antonio Nyman, Tuula A. Sjaastad, Ivar Christensen, Geir Carlson, Cathrine Rein |
| Copyright Year | 2019 |
| Description | Journal: Journal of Biological Chemistry Costameres are signaling hubs at the sarcolemma and important contact points between the extracellular matrix and cell interior, sensing and transducing biomechanical signals into a cellular response. The transmembrane proteoglycan syndecan-4 localizes to these attachment points and has been shown to be important in the initial stages of cardiac remodeling, but its mechanistic function in the heart remains insufficiently understood. Here, we sought to map the cardiac interactome of syndecan-4 to better understand its function and downstream signaling mechanisms. By combining two different affinity purification methods with MS analysis, we found that the cardiac syndecan-4 interactome consists of 21 novel and 29 previously described interaction partners. Nine of the novel partners were further validated to bind syndecan-4 in HEK293 cells (i.e. CAVIN1/PTRF, CCT5, CDK9, EIF2S1, EIF4B, MPP7, PARVB, PFKM, and RASIP). We also found that 19 of the 50 interactome partners bind differently to syndecan-4 in the left ventricle lysate from aortic-banded heart failure (ABHF) rats compared with SHAM-operated animals. One of these partners was the well-known mechanotransducer muscle LIM protein (MLP), which showed direct and increased binding to syndecan-4 in ABHF. Nuclear translocation is important in MLP-mediated signaling, and we found less MLP in the nuclear-enriched fractions from $syndecan-4^{−/−}$ mouse left ventricles but increased nuclear MLP when syndecan-4 was overexpressed in a cardiomyocyte cell line. In the presence of a cell-permeable syndecan-4–MLP disruptor peptide, the nuclear MLP level was reduced. These findings suggest that syndecan-4 mediates nuclear translocation of MLP in the heart. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552415/pdf http://www.jbc.org/content/294/22/8717.full.pdf |
| Ending Page | 8731 |
| Page Count | 15 |
| Starting Page | 8717 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.ra118.006423 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 22 |
| Volume Number | 294 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-05-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Cysteine and Glycine Rich Protein 3 (csrp3) Muscle Lim Protein (mlp) Nuclear Translocation Protein–protein Interaction |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
