Extracellular transglutaminase-2, nude or associated with astrocytic extracellular vesicles, modulates neuronal calcium homeostasis

Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines

“…In addition, inhibition of transamidating activity of TG2 pharmacologically showed reduced migration of metastatic PC3 cells suggesting that TG2 promotes cell migration through its cross-linking activity. We know that TG2 is present in the cytosol and in the nucleus [ 60 , 61 ], but it is also released from cells via extracellular vesicles [ 35 , 37 – 39 ] and here we have shown for the first time that the canonical form of TG2 is prominent in small extracellular vesicles of PC3 cells. Interestingly, we have found that EVs not only contain TG2 but also mucin isoforms in the membrane and intraluminal fractions that may be communicated from cell to cell.…”

“…EVs were isolated and characterised as previously described [ 39 ]. Briefly, cells were incubated in serum-free medium for 24 h. Conditioned medium was supplemented with protease inhibitors and serially centrifuged at 300 × g for 10 min (three times), 1200 × g for 20 min, 10,000 × g for 30 min to pellet large EVs and finally 110,000 × g for 70 min to pellet small EVs.…”

“…The proteome of EVs lysates and EVs membrane fractions were subjected to reduction, alkylation and trypsin digestion, then analysed by RP-HPLC-ESI-MS/MS using a TripleTOF 6600 mass spectrometer (SCIEX, Ontario, Canada) in data-dependent acquisition mode [ 38 ]. Density gradient fractionation was performed as previously described [ 39 ].…”

Molecular profiling of urinary extracellular vesicles in chronic kidney disease and renal fibrosis

“…This is a key point that warrants future scrutiny, especially as new tools allowing direct uEVs marker quantifications in biofluids without necessity to isolate uEVs have emerged and are available to the scientific community (e.g. Exoview platform, Tonoli et al, 2022 ).…”

A Multidisciplinary Approach Establishes a Link between Transglutaminase 2 and the Kv10.1 Voltage-Dependent K+ Channel in Breast Cancer

“…For this reason, we studied the impacts of TG2 inhibitors on membrane currents. Recently, interference by TG2 contained in exosomes was reported in L-type calcium channels, localized on the pre-and postsynaptic nerve terminals in the central nervous system [36], but in this study we focused on intracellular actions which are targetable to obtain antitumor effects [34].…”