scholarly journals Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species

2021 ◽  
Vol 22 (10) ◽  
pp. 5274
Author(s):  
Ivana Strazic Geljic ◽  
Paola Kucan Brlic ◽  
Lucija Musak ◽  
Dubravka Karner ◽  
Andreja Ambriović-Ristov ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Protein Complexes ◽  
Adaptor Protein ◽  
Cellular Protein ◽  
Immune Defense ◽  
Membrane Structures ◽  
Transport Pathways ◽  
Viral Propagation ◽  
Causative Agents ◽  
Mediate Cell

Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the immune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the conserved viral targets with many viruses possessing AP-interacting motifs. We present here different mechanisms of viral interference with AP complexes and the functional consequences that allow for efficient viral propagation and evasion of host immune defense. The ubiquity of this phenomenon is evidenced by the fact that there are representatives for AP interference in all major viral families, covered in this review. The best described examples are interactions of human immunodeficiency virus and human herpesviruses with AP complexes. Several other viruses, like Ebola, Nipah, and SARS-CoV-2, are pointed out as high priority disease-causative agents supporting the need for deeper understanding of virus-AP interplay which can be exploited in the design of novel antiviral therapies.

scholarly journals Phosphoserine acidic cluster motifs in the cytoplasmic domains of transmembrane proteins bind distinct basic regions on the μ subunits of clathrin adaptor protein complexes

2018 ◽  
Author(s):  
Rajendra Singh ◽  
Charlotte Stoneham ◽  
Christopher Lim ◽  
Xiaofei Jia ◽  
Javier Guenaga ◽  
...  
Keyword(s):  
Protein Trafficking ◽  
Transmembrane Proteins ◽  
Adaptor Protein ◽  
Cellular Protein ◽  
Membrane Lipid ◽  
Dependent Manner ◽  
Cytoplasmic Domains ◽  
Clathrin Adaptor ◽  
Hiv 1

AbstractProtein trafficking in the endosomal system involves the recognition of specific signals within the cytoplasmic domains (CDs) of transmembrane proteins by clathrin adaptors. One such signal is the phosphoserine acidic cluster (PSAC), the prototype of which is in the endoprotease Furin. How PSACs are recognized by clathrin adaptors has been controversial. We reported previously that HIV-1 Vpu, which modulates cellular immunoreceptors, contains a PSAC that binds to the µ subunits of clathrin adaptor protein (AP) complexes. Here, we show that the CD of Furin binds the µ subunits of AP-1 and AP-2 in a phosphorylation-dependent manner. Moreover, we identify a PSAC in a cytoplasmic loop of the cellular transmembrane Serinc3, an inhibitor of the infectivity of retroviruses. The two serines within the PSAC of Serinc3 are phosphorylated by casein kinase II and mediate interaction with the µ subunits in vitro. The sites of these serines vary among mammals in a manner consistent with host-pathogen conflict, yet the Serinc3-PSAC seems dispensible for anti-HIV activity and for counteraction by HIV-1 Nef. The CDs of Vpu, Furin, and the PSAC-containing loop of Serinc3 each bind the μ subunit of AP-2 (µ2) with similar affinities, but they appear to utilize different basic regions on µ2. The Serinc3 loop requires a region previously reported to bind the acidic plasma membrane lipid phosphatidylinositol-4,5-bisphosphate. These data suggest that the PSACs within different proteins recognize different basic regions on the µ surface, providing the potential to inhibit the activity of viral proteins without necessarily affecting cellular protein trafficking.

scholarly journals Adaptor protein complexes and intracellular transport

2014 ◽  
Vol 34 (4) ◽  
Author(s):  
Sang Yoon Park ◽  
Xiaoli Guo
Keyword(s):  
Membrane Trafficking ◽  
Intracellular Transport ◽  
Protein Complexes ◽  
Adaptor Protein ◽  
Inherited Disorders ◽  
Transport Pathways ◽  
Vesicular Carriers ◽  
Cargo Proteins ◽  
Intracellular Compartments ◽  
Secretory Transport

The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky–Pudlak syndrome) and HSP (hereditary spastic paraplegia).

scholarly journals Protein Trafficking or Cell Signaling: A Dilemma for the Adaptor Protein TOM1

2021 ◽  
Vol 9 ◽  
Author(s):  
Tiffany G. Roach ◽  
Heljä K. M. Lång ◽  
Wen Xiong ◽  
Samppa J. Ryhänen ◽  
Daniel G. S. Capelluto
Keyword(s):  
Cancer Progression ◽  
Protein Trafficking ◽  
Bacterial Infections ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Transmembrane Protein ◽  
Adaptor Protein ◽  
Endosomal Membrane ◽  
Protein Receptors ◽  
Cargo Sorting

Lysosomal degradation of ubiquitinated transmembrane protein receptors (cargo) relies on the function of Endosomal Sorting Complex Required for Transport (ESCRT) protein complexes. The ESCRT machinery is comprised of five unique oligomeric complexes with distinct functions. Target of Myb1 (TOM1) is an ESCRT protein involved in the initial steps of endosomal cargo sorting. To exert its function, TOM1 associates with ubiquitin moieties on the cargo via its VHS and GAT domains. Several ESCRT proteins, including TOLLIP, Endofin, and Hrs, have been reported to form a complex with TOM1 at early endosomal membrane surfaces, which may potentiate the role of TOM1 in cargo sorting. More recently, it was found that TOM1 is involved in other physiological processes, including autophagy, immune responses, and neuroinflammation, which crosstalk with its endosomal cargo sorting function. Alteration of TOM1 function has emerged as a phosphoinositide-dependent survival mechanism for bacterial infections and cancer progression. Based on current knowledge of TOM1-dependent cellular processes, this review illustrates how TOM1 functions in coordination with an array of protein partners under physiological and pathological scenarios.

scholarly journals Two Sides of the Coin: Ezrin/Radixin/Moesin and Merlin Control Membrane Structure and Contact Inhibition

2019 ◽  
Vol 20 (8) ◽  
pp. 1996 ◽  
Author(s):  
Katharine A. Michie ◽  
Adam Bermeister ◽  
Neil O. Robertson ◽  
Sophia C. Goodchild ◽  
Paul M. G. Curmi
Keyword(s):  
Actin Cytoskeleton ◽  
Protein Complexes ◽  
Membrane Vesicle ◽  
Contact Inhibition ◽  
Cell Junctions ◽  
Cellular Membranes ◽  
Membrane Structures ◽  
Cortical Actin ◽  
Erm Proteins ◽  
Structural Conservation

The merlin-ERM (ezrin, radixin, moesin) family of proteins plays a central role in linking the cellular membranes to the cortical actin cytoskeleton. Merlin regulates contact inhibition and is an integral part of cell–cell junctions, while ERM proteins, ezrin, radixin and moesin, assist in the formation and maintenance of specialized plasma membrane structures and membrane vesicle structures. These two protein families share a common evolutionary history, having arisen and separated via gene duplication near the origin of metazoa. During approximately 0.5 billion years of evolution, the merlin and ERM family proteins have maintained both sequence and structural conservation to an extraordinary level. Comparing crystal structures of merlin-ERM proteins and their complexes, a picture emerges of the merlin-ERM proteins acting as switchable interaction hubs, assembling protein complexes on cellular membranes and linking them to the actin cytoskeleton. Given the high level of structural conservation between the merlin and ERM family proteins we speculate that they may function together.

scholarly journals Adaptor Protein CD2AP and L-type Lectin LMAN2 Regulate Exosome Cargo Protein Trafficking through the Golgi Complex

2016 ◽  
Vol 291 (49) ◽  
pp. 25462-25475 ◽  
Author(s):  
Sang-Ho Kwon ◽  
Sekyung Oh ◽  
Marisa Nacke ◽  
Keith E. Mostov ◽  
Joshua H. Lipschutz
Keyword(s):  
Golgi Complex ◽  
Protein Trafficking ◽  
Adaptor Protein ◽  
Cargo Protein

Interaction with complement proteins and dendritic cells implicates LCCL domain-containing proteins (CCps) of malaria parasites in immunomodulation

2018 ◽  
Vol 475 (21) ◽  
pp. 3311-3314 ◽  
Author(s):  
Puran Singh Sijwali
Keyword(s):  
Dendritic Cells ◽  
Complement System ◽  
Protein Complexes ◽  
Immune Defense ◽  
Malaria Parasites ◽  
Classical Complement Pathway ◽  
Soluble Immune Complexes ◽  
Multimeric Protein ◽  
The Complement System

The evasion of host immune defense is critical for pathogens to invade, establish infection and perpetuate in the host. The complement system is one of the first lines of innate immune defense in humans that destroys pathogens in the blood circulation. Activation of the complement system through direct encounter with pathogens or some other agents leads to osmolysis of pathogens, clearance of soluble immune complexes and recruitment of lymphocytes at the site of activation. Although malaria parasites are not exposed to the complement system owing to their intracellular development for most part of their life cycle in the human host, the extracellular stages must face the complement system of human or mosquito or both. In a recent issue of the Biochemical Journal, Sharma et al. reported that Plasmodiumfalciparum LCCL domain-containing protein 1 (PfCCp1) inhibited activation of the classical complement pathway and down-regulated effector responses of dendritic cells, which implicate PfCCp1 and related proteins in immunomodulation of the host that likely benefits the parasite. PfCCp1 belongs to a multi-domain protein family that exists as multimeric protein complexes. It needs to be investigated whether PfCCp1 or its multimeric protein complexes have an immunomodulatory effect in vivo and on the mosquito complement system

scholarly journals An AP-3-dependent mechanism drives synaptic-like microvesicle biogenesis in pancreatic islet β-cells

2010 ◽  
Vol 299 (1) ◽  
pp. E23-E32 ◽  
Author(s):  
Arthur T. Suckow ◽  
Branch Craige ◽  
Victor Faundez ◽  
William J. Cain ◽  
Steven D. Chessler
Keyword(s):  
Synaptic Vesicle ◽  
Pancreatic Islet ◽  
Membrane Trafficking ◽  
Protein Complexes ◽  
Brefeldin A ◽  
Adaptor Protein ◽  
Β Cells ◽  
Β Cell ◽  
Subunit Expression ◽  
Bona Fide

Pancreatic islet β-cells contain synaptic-like microvesicles (SLMVs). The origin, trafficking, and role of these SLMVs are poorly understood. In neurons, synaptic vesicle (SV) biogenesis is mediated by two different cytosolic adaptor protein complexes, a ubiquitous AP-2 complex and the neuron-specific AP-3B complex. Mice lacking AP-3B subunits exhibit impaired GABAergic (inhibitory) neurotransmission and reduced neuronal vesicular GABA transporter (VGAT) content. Since β-cell maturation and exocytotic function seem to parallel that of the inhibitory synapse, we predicted that AP-3B-associated vesicles would be present in β-cells. Here, we test the hypothesis that AP-3B is expressed in islets and mediates β-cell SLMV biogenesis. A secondary aim was to test whether the sedimentation properties of INS-1 β-cell microvesicles are identical to those of bona fide SLMVs isolated from PC12 cells. Our results show that the two neuron-specific AP-3 subunits β3B and μ3B are expressed in β-cells, the first time these proteins have been found to be expressed outside the nervous system. We found that β-cell SLMVs share the same sedimentation properties as PC12 SLMVs and contain SV proteins that sort specifically to AP-3B-associated vesicles in the brain. Brefeldin A, a drug that interferes with AP-3-mediated SV biogenesis, inhibits the delivery of AP-3 cargoes to β-cell SLMVs. Consistent with a role for AP-3 in the biogenesis of GABAergic SLMV in β-cells, INS-1 cell VGAT content decreases upon inhibition of AP-3 δ-subunit expression. Our findings suggest that β-cells and neurons share molecules and mechanisms important for mediating the neuron-specific membrane trafficking pathways that underlie synaptic vesicle formation.

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