Changes in membrane lipids drive increased endocytosis following Fas ligation

Once activated, some surface receptors promote membrane movements that open new portals of endocytosis, in part to facilitate the internalization of their activated complexes. The prototypic death receptor Fas (CD95/Apo1) promotes a wave of enhanced endocytosis that induces a transient intermixing of endosomes with mitochondria in cells that require mitochondria to amplify death signaling. This initiates a global alteration in membrane traffic that originates from changes in key membrane lipids occurring in the endoplasmic reticulum (ER). We have focused the current study on specific lipid changes occurring early after Fas ligation. We analyzed the interaction between endosomes and mitochondria in Jurkat T cells by nanospray-Time-of-flight (ToF) Mass Spectrometry. Immediately after Fas ligation, we found a transient wave of lipid changes that drives a subpopulation of early endosomes to merge with mitochondria. The earliest event appears to be a decrease of phosphatidylcholine (PC), linked to a metabolic switch enhancing phosphatidylinositol (PI) and phosphoinositides, which are crucial for the formation of vacuolar membranes and endocytosis. Lipid changes occur independently of caspase activation and appear to be exacerbated by caspase inhibition. Conversely, inhibition or compensation of PC deficiency attenuates endocytosis, endosome-mitochondria mixing and the induction of cell death. Deficiency of receptor interacting protein, RIP, also limits the specific changes in membrane lipids that are induced by Fas activation, with parallel reduction of endocytosis. Thus, Fas activation rapidly changes the interconversion of PC and PI, which then drives enhanced endocytosis, thus likely propagating death signaling from the cell surface to mitochondria and other organelles

EVALUASI KESUKSESAN PENERAPAN SISTEM INFORMASI ADMINISTRASI SURAT MENYURAT(SIASY)MENGGUNAKAN METODE HOT-FIT(Studi Kasus: Fakultas Ekonomi dan Ilmu Sosial Uin Suska Riau)

Sistem Informasi Administrasi Surat Menyurat (SIASY) merupakan sistem informasi pelayananadministrasi surat menyurat berbasis website.SIASY ini dapat digunakan oleh mahasiswa, dosen,dan pegawai dalam mendapatkan informasi surat menyurat danpengajuan pembuatan surat,menyurat, sistem ini diharapkan dapat meningkatkan kinerja pegawai dan mahasiswa lebih efisienkedepannya.Pada penerapannya masih terdapat permasalahan yaitubelum semua pengguna yangmenggunakannya,masih rendahnya kontrol daripimpinan,fitur pengunduhan blangko dokumenskripsi tidak dapat dilakukan, tidak tersedia unduhanfileSOP,danmenu ganti password hanyadapat dilakukan sekali.Dalam menyelesaikan kendala tersebut dilakukanlah evaluasi denganmenggunakanHuman, Organization, Technology(HOT)FitModel, dimmana evaluasi didasarkanpadafeedbackdari pengguna dengan menyebarkan kuesioner kepada pengguna SIASY.Tujuanpenelitian ini adalah untuk melihattingkatkesuksesan penerapan SIASY, mengetahui hubunganantarafaktor-faktor kesuksesan, mengukur kesesuaian HOT-Fit.Untuk teknik analisis datamenggunakansoftware Structural Equation Modelling Partical Least Square(SEMPLS)dan alatpengolahan data yaitu SMARTPLS 3.0. Dari hasil pengujian hipotesis diperoleh fakta bahwasystem qualityberpengaruh terhadapsystem use,structure organizationberpengaruh terhadapuser satisfaction,system use berpengaruh terhadapnet benefit.Hasil dari penelitian inimenunjukan bahwa penerrapan SIASY pada Fakultas Ekonomi dan Ilmu Sosial Uin Suska Riaubelum sepenuhnya sukses karena masih terdapat tujuan dari penerapan SIASY belum tercapai.Dalam HOT Fit, kesuksesanpenerapan SIASY pada Fakultas Ekonomi dan Ilmu Sosial Uin SuskaRiau berada dalam tingkat 38% dan termasuk dalam kategori cukupbaik.Kata kunci:HOT-FitModel,SEMPLS, SIASY, SMARTPLS 3

Role of membrane environment and membrane-spanning protein regions in assembly and function of the Class II Major Histocompatibility complex

Class II Major Histocompatibility complex (MHC-II) is a polymorphic heterodimer that binds antigen-derived peptides and presents them on the surface of antigen presenting cells. This mechanism of antigen presentation leads to recognition by CD4 T-cells and T-cell activation, making it a critical element of adaptive immune response. For this reason, the structural determinants of MHC-II function have been of great interest for the past 30 years, resulting in a robust structural understanding of the extracellular regions of the complex. However, the membrane-localized regions have also been strongly implicated in protein-protein and protein-lipid interactions that facilitate Class II assembly, transport and function, and it is these regions that are the focus of this review. Here we describe studies that reveal the strong and selective interactions between the transmembrane domains of the MHC α, and invariant chains which, when altered, have broad reaching impacts on antigen presentation and Class II function. We also summarize work that clearly demonstrates the link between membrane lipid composition (particularly the presence of cholesterol) and MHC-II conformation, subsequent peptide binding, and downstream T-cell activation. We have integrated these studies into a comprehensive view of Class II transmembrane domain biology. [Abstract copyright: Copyright © 2018. Published by Elsevier Inc.

The microbiologist’s guide to membrane potential dynamics

All cellular membranes have the functionality of generating and maintaining the gradients of electrical and electrochemical potentials. Such potentials were generally thought to be an essential but homeostatic contributor to complex bacterial behaviors. Recent studies have revised this view, and we now know that bacterial membrane potential is dynamic and plays signaling roles in cell–cell interaction, adaptation to antibiotics, and sensation of cellular conditions and environments. These discoveries argue that bacterial membrane potential dynamics deserve more attention. Here, we review the recent studies revealing the signaling roles of bacterial membrane potential dynamics. We also introduce basic biophysical theories of the membrane potential to the microbiology community and discuss the needs to revise these theories for applications in bacterial electrophysiology

Membrane Fission: A Computational Complexity Perspective

Membrane fission is a process by which a biological membrane is split into two new ones in the manner that the content of the initial membrane is separated and distributed between the new membranes. Inspired by this biological phenomenon, membrane separation rules were considered in membrane computing. In this work, we investigate cell-like P systems with symport/antiport rules and membrane separation rules from a computational complexity perspective. Specifically, we establish a limit on the efficiency of such P systems which use communication rules of length at most two, and we prove the computational efficiency of this kind of models when using communication rules of length at most three. Hence, a sharp borderline between tractability and NP–hardness is provided in terms of the length of communication rules.Ministerio de Economía y Competitividad TIN2012-3743

Protein-induced membrane curvature changes membrane tension

Adsorption of proteins onto membranes can alter the local membrane curvature. This phenomenon has been observed in biological processes such as endocytosis, tubulation and vesiculation. However, it is not clear how the local surface properties of the membrane, such as membrane tension, change in response to protein adsorption. In this paper, we show that the classical elastic model of lipid membranes cannot account for simultaneous changes in shape and membrane tension due to protein adsorption in a local region, and a viscous-elastic formulation is necessary to fully describe the system. Therefore, we develop a viscous-elastic model for inhomogeneous membranes of the Helfrich type. Using the new viscous-elastic model, we find that the lipids flow to accommodate changes in membrane curvature during protein adsorption. We show that, at the end of protein adsorption process, the system sustains a residual local tension to balance the difference between the actual mean curvature and the imposed spontaneous curvatures. This change in membrane tension can have a functional impact in many biological phenomena where proteins interact with membranes.Comment: 15 pages, 5 figure

Translocation and insertion of precursor proteins into isolated outer membranes of mitochondria

Nuclear-encoded proteins destined for mitochondria must cross the outer or both outer and inner membranes to reach their final sub- mitochondrial locations. While the inner membrane can translocate preproteins by itself, it is not known whether the outer membrane also contains an endogenous protein translocation activity which can function independently of the inner membrane. To selectively study the protein transport into and across the outer membrane of Neurospora crassa mitochondria, outer membrane vesicles were isolated which were sealed, in a right-side-out orientation, and virtually free of inner membranes. The vesicles were functional in the insertion and assembly of various outer membrane proteins such as porin, MOM19, and MOM22. Like with intact mitochondria, import into isolated outer membranes was dependent on protease-sensitive surface receptors and led to correct folding and membrane integration. The vesicles were also capable of importing a peripheral component of the inner membrane, cytochrome c heme lyase (CCHL), in a receptor-dependent fashion. Thus, the protein translocation machinery of the outer mitochondrial membrane can function as an independent entity which recognizes, inserts, and translocates mitochondrial preproteins of the outer membrane and the intermembrane space. In contrast, proteins which have to be translocated into or across the inner membrane were only specifically bound to the vesicles, but not imported. This suggests that transport of such proteins involves the participation of components of the intermembrane space and/or the inner membrane, and that in these cases the outer membrane translocation machinery has to act in concert with that of the inner membrane

Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.

Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing