title: Characterization of distinct sub-cellular location of transglutaminase type II: changes in intracellular distribution in physiological and pathological states.
abstract: Transglutaminase type II (TG2) is a pleiotropic enzyme that exhibits various activities unrelated to its originally identified functions. Apart from post-translational modifications of proteins (peculiar to the transglutaminase family enzymes), TG2 is involved in diverse biological functions, including cell death, signaling, cytoskeleton rearrangements, displaying enzymatic activities, G-protein and non-enzymatic biological functions. It is involved in a variety of human diseases such as celiac disease, diabetes, neurodegenerative diseases, inflammatory disorders and cancer. Regulatory mechanisms might exist through which cells control multifunctional protein expression as a function of their sub-cellular localization. The definition of the tissue and cellular distribution of such proteins is important for the determination of their function(s). We investigate the sub-cellular localization of TG2 by confocal and immunoelectron microscopy techniques in order to gain an understanding of its properties. The culture conditions of human sarcoma cells (2fTGH cells), human embryonic kidney cells (HEK293(TG)) and human neuroblastoma cells (SK-n-BE(2)) are modulated to induce various stimuli. Human tissue samples of myocardium and gut mucosa (diseased and healthy) are also analyzed. Immuno-gold labeling indicates that TG2 is localized in the nucleus, mitochondria and endoplasmic reticulum under physiological conditions but that this is not a stable association, since different locations or different amounts of TG2 can be observed depending on stress stimuli or the state of activity of the cell. We describe a possible unrecognized location of TG2. Our findings thus provide useful insights regarding the functions and regulation of this pleiotropic enzyme.
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Manuela
authors.initials: M
authors.lastname: D'Eletto
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Farrace
authors.forename: Carlo
authors.initials: C
authors.lastname: Rodolfo
authors.forename: Franca
authors.initials: F
authors.lastname: Del Nonno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Laura
authors.initials: L
authors.lastname: Falasca
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004317:Doxorubicin / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000648:ultrastructure; D057809:HEK293 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000648:ultrastructure; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology*; D008954:Models, Biological; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009447:Neuroblastoma / Q000473:pathology / Q000648:ultrastructure; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D021381:Protein Transport / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D011503:Transglutaminases / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D004317:Doxorubicin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins