Dysbindin deficiency Alters Cardiac BLOC-1 Complex and Myozap Levels in Mice
| Autor: | Norbert Frey, Alexandra Rosskopf, Lynn Christen, Nesrin Schmiedel, Matthias Eden, Ankush Borlepawar, Derk Frank, Renate Lüllmann-Rauch, Ashraf Yusuf Rangrez |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Muted 0301 basic medicine Serum Response Factor Vesicular Transport Proteins Muscle Proteins Cardiomegaly Biology Article Mice 03 medical and health sciences Cytosol 0302 clinical medicine In vivo Organelle medicine Animals Myocytes Cardiac lcsh:QH301-705.5 Phenylephrine Mice Knockout Pallidin Organelle Biogenesis cardiac hypertrophy Dysbindin Intracellular Signaling Peptides and Proteins Intron Hypertrophy General Medicine In vitro Pathophysiology Cell biology Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation lcsh:Biology (General) Myozap Schizophrenia rhoA GTP-Binding Protein 030217 neurology & neurosurgery Biogenesis Protein Binding Signal Transduction medicine.drug |
| Zdroj: | Cells, Vol 9, Iss 2390, p 2390 (2020) Cells Volume 9 Issue 11 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9112390 |
| Popis: | Dysbindin, a schizophrenia susceptibility marker and an essential constituent of BLOC-1 (biogenesis of lysosome-related organelles complex-1), has recently been associated with cardiomyocyte hypertrophy through the activation of Myozap-RhoA-mediated SRF signaling. We employed sandy mice (Dtnbp1_KO), which completely lack Dysbindin protein because of a spontaneous deletion of introns 5&ndash 7 of the Dtnbp1 gene, for pathophysiological characterization of the heart. Unlike in vitro, the loss-of-function of Dysbindin did not attenuate cardiac hypertrophy, either in response to transverse aortic constriction stress or upon phenylephrine treatment. Interestingly, however, the levels of hypertrophy-inducing interaction partner Myozap as well as the BLOC-1 partners of Dysbindin like Muted and Pallidin were dramatically reduced in Dtnbp1_KO mouse hearts. Taken together, our data suggest that Dysbindin&rsquo s role in cardiomyocyte hypertrophy is redundant in vivo, yet essential to maintain the stability of its direct interaction partners like Myozap, Pallidin and Muted. |
| Databáze: | OpenAIRE |
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