Transglutaminases (TGs) play essential intracellular and extracellular roles by covalently cross-linking many proteins. Drosophila TG is encoded by one gene and has two alternative splicing-derived isoforms, TG-A and TG-B, which contain distinct N-terminal 46- and 38-amino acid sequences, respectively. The TGs identified to date do not have a typical endoplasmic reticulum (ER)-signal peptide, and the molecular mechanisms of their secretion under physiologic conditions are unclear. Immunocytochemistry revealed that TG-A localizes to multivesicular-like structures, whereas TG-B localizes to the cytosol. We also found that TG-A, but not TG-B, was modified concomitantly by N-myristoylation and S-palmitoylation, and N-myristoylation was a pre-requisite for S-palmitoylation. Moreover, TG-A, but not TG-B, was secreted in response to calcium signaling induced by Ca2+ ionophores and uracil, a pathogenic bacteria-derived substance. Brefeldin A and monensin, inhibitors of the ER/Golgi-mediated conventional pathway, did not suppress TG-A secretion, whereas inhibition of S-palmitoylation by 2-bromopalmitate blocked TG-A secretion. Ultracentrifugation, electron microscopy analyses, and treatments with inhibitors of multivesicular body formation revealed that TG-A was secreted via exosomes together with co-transfected mammalian CD63, an exosomal marker, and the secreted TG-A was taken up by other cells. The 8-residue N-terminal fragment of TG-A containing the fatty acylation sites was both necessary and sufficient for the exosome-dependent secretion of TG-A. In conclusion, TG-A is secreted through an unconventional ER/Golgi-independent pathway involving two types of fatty acylations and exosomes.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2pOKrjp
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
In this paper, we combine the reduced-form model with the structural model to discuss the European vulnerable option pricing. We define that...
-
Publication date: May 2017 Source: Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5 http://ift.tt/2p88NST
-
BACKGROUND AND PURPOSE: The neonatal brain has active energy metabolism, and glucose oxidation is the major energy source of brain tissue...
-
Abstract Food allergy is estimated to affect approximately 8% of children in the USA. This is a disease without any known treatment or cur...
-
Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibilit...
-
Abstract Background The STOPBANG questionnaire is used to predict the presence of obstructive sleep apnea (OSA). We sought to assess the...
-
Abstract Objective To compare hepatocellular phase imaging after intravenous gadoxetate disodium with other MRI pulse sequences and with e...
-
Abstract This is the sixth in a series of papers where we bring collaborating mycologists together to produce a set of notes of several tax...
-
An enormous and probably definitive guide to the life, times and genius of Alan Turing captures his extraordinary diversity for the first t...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου