Dysbindin deficiency Alters Cardiac BLOC-1 Complex and Myozap Levels in Mice.

Abstract	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 5-7 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'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.
Authors	Ankush Borlepawar, Nesrin Schmiedel, Matthias Eden, Lynn Christen, Alexandra Rosskopf, Derk Frank, Renate Lüllmann-Rauch, Norbert Frey, Ashraf Yusuf Rangrez
Journal	Cells (Cells) Vol. 9 Issue 11 (10 31 2020) ISSN: 2073-4409 [Electronic] Switzerland
PMID	33142804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Bloc1s6 protein, mouse Dtnbp1 protein, mouse Dysbindin Intracellular Signaling Peptides and Proteins Muscle Proteins Myozap protein, mouse Serum Response Factor Vesicular Transport Proteins muted protein, mouse rhoA GTP-Binding Protein
Topics	Animals Cardiomegaly (genetics, metabolism) Cytosol (metabolism) Dysbindin (genetics, metabolism) Gene Expression Regulation Hypertrophy (physiopathology) Intracellular Signaling Peptides and Proteins (metabolism) Male Mice Mice, Inbred C57BL Mice, Knockout Muscle Proteins (metabolism) Myocytes, Cardiac (metabolism) Organelle Biogenesis Protein Binding Schizophrenia (genetics, metabolism) Serum Response Factor (metabolism) Signal Transduction Vesicular Transport Proteins (metabolism) rhoA GTP-Binding Protein (metabolism)

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