Crucial role for the LSP1–myosin1e bimolecular complex in the regulation of Fcγ receptor–driven phagocytosis
نویسندگان
چکیده
Actin cytoskeleton remodeling is fundamental for Fcγ receptor-driven phagocytosis. In this study, we find that the leukocyte-specific protein 1 (LSP1) localizes to nascent phagocytic cups during Fcγ receptor-mediated phagocytosis, where it displays the same spatial and temporal distribution as the actin cytoskeleton. Down-regulation of LSP1 severely reduces the phagocytic activity of macrophages, clearly demonstrating a crucial role for this protein in Fcγ receptor-mediated phagocytosis. We also find that LSP1 binds to the class I molecular motor myosin1e. LSP1 interacts with the SH3 domain of myosin1e, and the localization and dynamics of both proteins in nascent phagocytic cups mirror those of actin. Furthermore, inhibition of LSP1-myosin1e and LSP1-actin interactions profoundly impairs pseudopodial formation around opsonized targets and their subsequent internalization. Thus the LSP1-myosin1e bimolecular complex plays a pivotal role in the regulation of actin cytoskeleton remodeling during Fcγ receptor-driven phagocytosis.
منابع مشابه
بررسی ارتباط پلی مرفیسم FC? RIIA با بیماری بروسلوز
Background and purpose: Brucellosis is a major bacterial zoonosis of global importance. Effective host defence against brucella depends on immunoglobulin G-mediated phagocytosis of the bacteria and it has been shown that the FC RIIA polymorphism (FCγ RIIA-R131 vs FCγ RIIA –H131) determines the capacity of immunoglobulin G-mediated phagocytosis via this receptor. The aim of this study was to e...
متن کاملPhagocytosis Enhances Lysosomal and Bactericidal Properties by Activating the Transcription Factor TFEB
Macrophages internalize pathogens through phagocytosis, entrapping them into organelles called phagosomes. Phagosomes then fuse with lysosomes to mature into phagolysosomes, acquiring an acidic and hydrolytic lumen that kills the pathogens. During an ongoing infection, macrophages can internalize dozens of bacteria. Thus, we hypothesized that an initial round of phagocytosis might boost lysosom...
متن کاملRole of Adenosine receptor in lung cancer
Summary: Adenosine through adenosine receptor have a crucial role in biology of lung cancer. Recent study indicated adenosine receptors have a crucial role in various aspect of lung cancer from cell growth and metastasis to modulation of apoptosis and it could be considered as a potential candidate for treatment of the lung cancer.
متن کاملIntegrins Form an Expanding Diffusional Barrier that Coordinates Phagocytosis
Phagocytosis is initiated by lateral clustering of receptors, which in turn activates Src-family kinases (SFKs). Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. We investigated how the major phosphatase CD45 is excluded from contact sites, using single-molecule tracking. The mobility of CD45 increased markedly upon engagement of Fcγ receptors...
متن کاملUp-regulation of TLR2 and TLR4 in high mobility group Box1-stimulated macrophages in pulpitis patients
Objective(s): High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from p...
متن کامل