title: Rint1 inactivation triggers genomic instability, ER stress and autophagy inhibition in the brain.
abstract: Endoplasmic reticulum (ER) stress, defective autophagy and genomic instability in the central nervous system are often associated with severe developmental defects and neurodegeneration. Here, we reveal the role played by Rint1 in these different biological pathways to ensure normal development of the central nervous system and to prevent neurodegeneration. We found that inactivation of Rint1 in neuroprogenitors led to death at birth. Depletion of Rint1 caused genomic instability due to chromosome fusion in dividing cells. Furthermore, Rint1 deletion in developing brain promotes the disruption of ER and Cis/Trans Golgi homeostasis in neurons, followed by ER-stress increase. Interestingly, Rint1 deficiency was also associated with the inhibition of the autophagosome clearance. Altogether, our findings highlight the crucial roles of Rint1 in vivo in genomic stability maintenance, as well as in prevention of ER stress and autophagy.
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg and Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Grigaravicius
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg and Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Kaminska
authors.affiliation: Institute of Human Genetics, University Hospital Jena, Friedrich Schiller University, Jena, Germany.
authors.forename: C A
authors.initials: CA
authors.lastname: Hübner
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: McKinnon
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg and Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.|Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg and Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
authors.forename: P-O
authors.initials: PO
authors.lastname: Frappart
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D042822:Genomic Instability; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D008938:Mitosis; D058953:Neural Stem Cells / Q000502:physiology; D061251:Primary Cell Culture; D011689:Purkinje Cells / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C521730:RINT-1 protein, mouse; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins