Author/Editor     Farkas, Zsolt; Petrič, Metka; Liu, Xianghua; Herit, Floriane; Rajnavölgyi, Éva; Szondy, Zsuzsa; Budai, Zsófia; Orbán, Tamás I.; Sára, Sándor; Mehta, Anil
Title     The nucleoside diphosphate kinase NDK-1/NME1 promotes phagocytosis in concert with DYN-1/Dynamin
Type     članek
Vol. and No.     Letnik 33, št. 10
Publication year     2019
Volume     str. 11606-11614
ISSN     0892-6638 - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Language     eng
Abstract     Phagocytosis of various targets, such as apoptotic cells or opsonized pathogens, by macrophages is co-ordinated by a complex signaling network initiated by distinct phagocytic receptors. Despite the different initial sig-naling pathways, each pathway ends up regulating the actin cytoskeletal network, phagosome formation and closure,and phagosome maturation leading to degradation of the engulfed particle. Herein, we describe a new phagocyticfunction for the nucleoside diphosphate kinase 1 (NDK-1), the nematode counterpart of the first identified metastasisinhibitor NM23-H1 (nonmetastatic clone number 23) nonmetastatic clone number 23 or nonmetastatic isoform 1 (NME1).We reveal by coimmunoprecipitation, Duolink proximity ligation assay, and mass spectrometry that NDK-1/NME1works in a complex with DYN-1/Dynamin (Caenorhabditis elegans/human homolog proteins), which is essential forengulfment and phagosome maturation. Time-lapse microscopy shows that NDK-1 is expressed on phagosomal surfacesduring cell corpse clearance in the same time window as DYN-1. Silencing of NM23-M1 in mouse bone marrow-derivedmacrophages resulted in decreased phagocytosis of apoptotic thymocytes. In human macrophages, NM23-H1 andDynamin are corecruited at sites of phagosome formation in F-actin-rich cups. In addition, NM23-H1 was required forefficient phagocytosis. Together, our data demonstratethat NDK-1/NME1 is an evolutionarily conserved element ofsuccessful phagocytosis.
Keywords     metastasis inhibitor
apoptotic clearance
phagosome formation
zaviralec metastaz
apoptotični očistek
tvorba fagosomov