| First Author | Naito D | Year | 2015 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 309 |
| Issue | 12 | Pages | H2127-36 |
| PubMed ID | 26497963 | Mgi Jnum | J:230668 |
| Mgi Id | MGI:5763521 | Doi | 10.1152/ajpheart.00446.2015 |
| Citation | Naito D, et al. (2015) The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking of caveolin-3 in cardiomyocytes. Am J Physiol Heart Circ Physiol 309(12):H2127-36 |
| abstractText | Muscle-restricted coiled-coil protein (MURC), also referred to as cavin-4, is a member of the cavin family that works cooperatively with caveolins in caveola formation and function. Cavins are cytoplasmic proteins with coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, and its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/cavin-4 gene have been identified in patients with dilated cardiomyopathy. In the present study, we show the role of MURC/cavin-4 as a caveolar component in the heart. In H9c2 cells, MURC/cavin-4 was localized at the plasma membrane, whereas a MURC/cavin-4 mutant lacking the coiled-coil domain (DeltaCC) was primarily localized to the cytoplasm. DeltaCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. Additionally, although DeltaCC did not alter Cav3 mRNA expression, DeltaCC decreased the Cav3 protein level. MURC/cavin-4 and DeltaCC similarly induced cardiomyocyte hypertrophy; however, DeltaCC showed higher hypertrophy-related fetal gene expression than MURC/cavin-4. DeltaCC induced ERK activation in cardiomyocytes. Transgenic mice expressing DeltaCC in the heart (DeltaCC-Tg mice) showed impaired cardiac function accompanied by cardiomyocyte hypertrophy and marked interstitial fibrosis. Hearts from DeltaCC-Tg mice showed a reduction of the Cav3 protein level and activation of ERK. These results suggest that MURC/cavin-4 requires its coiled-coil domain to target the plasma membrane and to stabilize Cav3 at the plasma membrane of cardiomyocytes and that MURC/cavin-4 functions as a crucial caveolar component to regulate cardiac function. |
