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oai:repisalud.isciii.es:20.500.12105/252522024-10-23T10:07:12Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16958

00925njm 22002777a 4500 dc Jiménez-González, Víctor author Ogalla-García, Elena author García-Quintanilla, Meritxell author García-Quintanilla, Albert author 2019-08-16 The Glutamate Receptor Ionotropic NMDA-Associated Protein 1 (GRINA) belongs to the Lifeguard family and is involved in calcium homeostasis, which governs key processes, such as cell survival or the release of neurotransmitters. GRINA is mainly associated with membranes of the endoplasmic reticulum, Golgi, endosome, and the cell surface, but its presence in the nucleus has not been explained yet. Here we dissect, with the help of different software tools, the potential roles of GRINA in the cell and how they may be altered in diseases, such as schizophrenia or celiac disease. We describe for the first time that the cytoplasmic N-terminal half of GRINA (which spans a Proline-rich domain) contains a potential DNA-binding sequence, in addition to cleavage target sites and probable PY-nuclear localization sequences, that may enable it to be released from the rest of the protein and enter the nucleus under suitable conditions, where it could participate in the transcription, alternative splicing, and mRNA export of a subset of genes likely involved in lipid and sterol synthesis, ribosome biogenesis, or cell cycle progression. To support these findings, we include additional evidence based on an exhaustive review of the literature and our preliminary data of the protein-protein interaction network of GRINA. 10.3390/ijms20164005 1422-0067 International journal of molecular sciences http://hdl.handle.net/10668/14411 31426446 https://hdl.handle.net/20.500.12105/25252 GRINA/TMBIM3/LFG1 Proline-rich domain Alternative splicing Calcium homeostasis Endoplasmic reticulum stress Endosome-to-Golgi retrieval Interactome Nucleolus Sterol Vesicle Deciphering GRINA/Lifeguard1: Nuclear Location, Ca2+ Homeostasis and Vesicle Transport.