Genomes and Genes
vesicular transport adaptor proteins
Summary: A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.
- Joshi A, Garg H, Nagashima K, Bonifacino J, Freed E. GGA and Arf proteins modulate retrovirus assembly and release. Mol Cell. 2008;30:227-38 pubmed publisher..These findings identify the GGA proteins as modulators of HIV-1 release and the Arf proteins as critical cellular cofactors in retroviral Gag trafficking to the plasma membrane. ..
- Kagan J, Su T, Horng T, Chow A, Akira S, Medzhitov R. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008;9:361-8 pubmed publisher..Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location. ..
- Zeevaert R, Foulquier F, Cheillan D, Cloix I, Guffon N, Sturiale L, et al. A new mutation in COG7 extends the spectrum of COG subunit deficiencies. Eur J Med Genet. 2009;52:303-5 pubmed publisher..In comparison to the previously described patients with a different COG7 mutation, intrauterine growth retardation and dysmorphic features were absent and there was a longer survival. ..
- Zeevaert R, Foulquier F, Jaeken J, Matthijs G. Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation. Mol Genet Metab. 2008;93:15-21 pubmed..Among 35 CDG-II patients we found 5 patients with a COG defect. COG defects are a novel group of CDG-II with deficient N- as well as O-glycosylation. ..
- Uh A, Nicholson R, Gonzalez G, Simmons C, GOMBART A, Smith R, et al. Lipopolysaccharide stimulation of trophoblasts induces corticotropin-releasing hormone expression through MyD88. Am J Obstet Gynecol. 2008;199:317.e1-6 pubmed publisher..DN-MyD88, but not DN-TRIF, blocked the LPS-induced CRH expression. The cAMP response element did not play a role in LPS-induced CRH expression. Toll-like receptor signaling 4 may induce placental CRH expression through MyD88. ..
- Giraudo C, Garcia Diaz A, Eng W, Yamamoto A, Melia T, Rothman J. Distinct domains of complexins bind SNARE complexes and clamp fusion in vitro. J Biol Chem. 2008;283:21211-9 pubmed publisher..These correspond closely to results from in vivo experiments, providing further validation of the physiological relevance of the flipped SNARE system. ..
- Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, et al. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009;11:385-96 pubmed publisher..These data suggest that the Beclin 1-hVps34 complex functions in two different steps of autophagy by altering the subunit composition. ..
- Liu Z, Zheng Y. A requirement for epsin in mitotic membrane and spindle organization. J Cell Biol. 2009;186:473-80 pubmed publisher..Our study of epsin provides evidence that mitotic membrane organization influences spindle integrity. ..
- Cai H, Reim K, Varoqueaux F, Tapechum S, Hill K, Sørensen J, et al. Complexin II plays a positive role in Ca2+-triggered exocytosis by facilitating vesicle priming. Proc Natl Acad Sci U S A. 2008;105:19538-43 pubmed publisher..Our results show that CPXs regulate the size of the primed vesicle pools and have a positive role in Ca(2+)-triggered exocytosis. ..
- Xue M, Stradomska A, Chen H, Brose N, Zhang W, Rosenmund C, et al. Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system. Proc Natl Acad Sci U S A. 2008;105:7875-80 pubmed publisher..Our results demonstrate that at mammalian central nervous system synapses, Cplxs facilitate neurotransmitter release and do not simply act as inhibitory clamps of the synaptic vesicle fusion machinery. ..
- De Luca A, Montagnoli C, Zelante T, Bonifazi P, Bozza S, Moretti S, et al. Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc. J Immunol. 2007;179:5999-6008 pubmed..This is the first study to show that the same tryptophan catabolites can foster dendritic cell-supported generation of Foxp3(+) cells and mediate, at the same time, inhibition of RORgammat-expressing T cells. ..
- ..For instance, it has been demonstrated that Sortilin partakes in the transduction of proapoptotic effects, and there is converging biochemical and genetic evidence that implies that SorLA is an Alzheimer's disease risk factor. ..
- Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19:5360-72 pubmed publisher..These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways. ..
- Smith R, Lupashin V. Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation. Carbohydr Res. 2008;343:2024-31 pubmed publisher..These pathologies involve a change in structural Golgi phenotype and function. Recent results indicate that down-regulation of COG function results in the resident Golgi glycosyltransferases/glycosidases to be mislocalized or degraded. ..
- Maximov A, Tang J, Yang X, Pang Z, Sudhof T. Complexin controls the force transfer from SNARE complexes to membranes in fusion. Science. 2009;323:516-21 pubmed publisher..Thus, complexin probably activates and clamps the force transfer from assembled trans-SNARE complexes onto fusing membranes. ..
- Kenny E, O Neill L. Signalling adaptors used by Toll-like receptors: an update. Cytokine. 2008;43:342-9 pubmed publisher..These advances confirm the importance for the TIR domain-containing adapters in host defence and inflammation. ..
- Sun Y, Shestakova A, Hunt L, Sehgal S, Lupashin V, Storrie B. Rab6 regulates both ZW10/RINT-1 and conserved oligomeric Golgi complex-dependent Golgi trafficking and homeostasis. Mol Biol Cell. 2007;18:4129-42 pubmed..We conclude that Rab6 regulates distinct Golgi trafficking pathways involving two separate protein complexes: ZW10/RINT-1 and COG. ..
- Weber A, Kirejczyk Z, Besch R, Potthoff S, Leverkus M, Hacker G. Proapoptotic signalling through Toll-like receptor-3 involves TRIF-dependent activation of caspase-8 and is under the control of inhibitor of apoptosis proteins in melanoma cells. Cell Death Differ. 2010;17:942-51 pubmed publisher..These results indicate that the proapoptotic activity of TLR3/TRIF/caspase-8 in melanoma cells is under the control of IAPs, and the use of novel Smac mimetics might be a feasible approach to target melanoma. ..
- Shen H, Tesar B, Walker W, Goldstein D. Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation. J Immunol. 2008;181:1849-58 pubmed..In sum, in our experimental systems, TRIF signaling plays a more important role in LPS-induced macrophage activation than in DC activation. ..
- Yoon T, Lu X, Diao J, Lee S, Ha T, Shin Y. Complexin and Ca2+ stimulate SNARE-mediated membrane fusion. Nat Struct Mol Biol. 2008;15:707-13 pubmed publisher..We suggest that SNARE complexes, complexins and phospholipids collectively form a complex substrate for Ca(2+) and Ca(2+)-sensing fusion effectors in neurotransmitter release. ..
- Zeevaert R, Foulquier F, Dimitrov B, Reynders E, Van Damme Lombaerts R, Simeonov E, et al. Cerebrocostomandibular-like syndrome and a mutation in the conserved oligomeric Golgi complex, subunit 1. Hum Mol Genet. 2009;18:517-24 pubmed publisher..We anticipate further genetic heterogeneity because no mutations in COG1 were found in two additional patients with a CCMS. ..
- Miller S, Collins B, McCoy A, Robinson M, Owen D. A SNARE-adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles. Nature. 2007;450:570-4 pubmed..We propose that conceptually similar but mechanistically different interactions will direct the post-Golgi trafficking of many SNAREs. ..
- Kawahara T, Lambeth J. Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes. BMC Evol Biol. 2007;7:178 pubmed..This approach provides clues for understanding the evolution of biochemical and physiological functions for regulatory-subunit-dependent Nox enzymes. ..
- Xue M, Reim K, Chen X, Chao H, Deng H, Rizo J, et al. Distinct domains of complexin I differentially regulate neurotransmitter release. Nat Struct Mol Biol. 2007;14:949-58 pubmed
- Dorfman J, Macara I. STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7. Mol Biol Cell. 2008;19:1614-26 pubmed publisher..These results identify a multifactored mechanism to control LKB1 localization, and they suggest that the STRADbeta-LKB1 complex might possess unique functions in the nucleus. ..
- Paesold Burda P, Maag C, Troxler H, Foulquier F, Kleinert P, Schnabel S, et al. Deficiency in COG5 causes a moderate form of congenital disorders of glycosylation. Hum Mol Genet. 2009;18:4350-6 pubmed publisher..This case demonstrates that COG deficiency and thereby CDG must be taken into consideration even in children presenting mild neurological impairments. ..
- Shigeoka A, Holscher T, King A, Hall F, Kiosses W, Tobias P, et al. TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J Immunol. 2007;178:6252-8 pubmed..We conclude that TLR2 protein is constitutively expressed in the kidney and plays an important role in the pathogenesis of acute ischemic injury by signaling both MyD88-dependent and MyD88-independent pathways. ..
- O Neill L, Bowie A. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7:353-64 pubmed..These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling. ..
- Flower T, Clark Dixon C, Metoyer C, Yang H, Shi R, Zhang Z, et al. YGR198w (YPP1) targets A30P alpha-synuclein to the vacuole for degradation. J Cell Biol. 2007;177:1091-104 pubmed..Our data reveal that YPP1 mediates the trafficking of A30P to the vacuole via the endocytic pathway. ..
- Dergai O, Novokhatska O, Dergai M, Skrypkina I, Tsyba L, Moreau J, et al. Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits. Biochem Biophys Res Commun. 2010;402:408-13 pubmed publisher..These findings expand the role of ITSN1 as a scaffolding molecule bringing together components of endocytic complexes. ..
- Mayer Barber K, Barber D, Shenderov K, White S, Wilson M, Cheever A, et al. Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol. 2010;184:3326-30 pubmed publisher..Together our findings reveal a major role for IL-1beta in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1. ..
- Brady R, Wen Y, O Halloran T. The ENTH and C-terminal domains of Dictyostelium epsin cooperate to regulate the dynamic interaction with clathrin-coated pits. J Cell Sci. 2008;121:3433-44 pubmed publisher..Our results support a model where the ENTH domain coordinates with the clathrin-binding C-terminal domain to allow a dynamic interaction of epsin with coated pits...
- Nerren J, Swaggerty C, MacKinnon K, Genovese K, He H, Pevzner I, et al. Differential mRNA expression of the avian-specific toll-like receptor 15 between heterophils from Salmonella-susceptible and -resistant chickens. Immunogenetics. 2009;61:71-7 pubmed publisher..These data indicate that differences in the gene expression of TLR 15 by heterophils likely accounts for some of the observed differences between the lines in their susceptibility to infection...
- Chen K, Huang J, Liu Y, Gong W, Cui Y, Wang J. Synergy of TRIF-dependent TLR3 and MyD88-dependent TLR7 in up-regulating expression of mouse FPR2, a promiscuous G-protein-coupled receptor, in microglial cells. J Neuroimmunol. 2009;213:69-77 pubmed publisher..Our results indicated that RNA virus infection may actively participate in the pathogenic processes of brain inflammation and neurodegenerative diseases by TLR3- and TLR7-mediated TRIF-dependent and MyD88-dependent signaling pathways. ..
- Rautou P, Cazals Hatem D, Moreau R, Francoz C, Feldmann G, Lebrec D, et al. Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy. Gastroenterology. 2008;135:840-8, 848.e1-3 pubmed publisher..Our findings show that starvation-induced autophagy in the human liver may be involved in liver cell death during anorexia nervosa, even though other mechanisms of liver cell damage could also play a role. ..
- Sebbagh M, Santoni M, Hall B, Borg J, Schwartz M. Regulation of LKB1/STRAD localization and function by E-cadherin. Curr Biol. 2009;19:37-42 pubmed publisher..The LKB1 complex therefore appears to function downstream of E-cadherin in tumor suppression. ..
- Wilson N, Young L, Kupresanin F, Naik S, Vremec D, Heath W, et al. Normal proportion and expression of maturation markers in migratory dendritic cells in the absence of germs or Toll-like receptor signaling. Immunol Cell Biol. 2008;86:200-5 pubmed
- Biswas S, Bist P, Dhillon M, Kajiji T, del Fresno C, Yamamoto M, et al. Role for MyD88-independent, TRIF pathway in lipid A/TLR4-induced endotoxin tolerance. J Immunol. 2007;179:4083-92 pubmed..Together, these observations constitute evidence for a role of the TRIF/IFN-beta pathway in the regulation of lipid A/TLR4-mediated endotoxin homotolerance. ..
- Canuel M, Lefrancois S, Zeng J, Morales C. AP-1 and retromer play opposite roles in the trafficking of sortilin between the Golgi apparatus and the lysosomes. Biochem Biophys Res Commun. 2008;366:724-30 pubmed..We also demonstrate that the interaction of sortilin with retromer occurs through a YXXPhi site in its cytosolic tail. In conclusion, our observations indicate that retromer and AP-1 play opposite roles in the trafficking of sortilin. ..
- Kumar H, Koyama S, Ishii K, Kawai T, Akira S. Cutting edge: cooperation of IPS-1- and TRIF-dependent pathways in poly IC-enhanced antibody production and cytotoxic T cell responses. J Immunol. 2008;180:683-7 pubmed..Taken together, these results demonstrate that the adjuvant effects of poly IC require a cooperative activation of TLR and cytoplasmic RNA helicase pathways. ..
- Al Shawi R, Hafner A, Olsen J, Olson J, Chun S, Raza S, et al. Neurotoxic and neurotrophic roles of proNGF and the receptor sortilin in the adult and ageing nervous system. Eur J Neurosci. 2008;27:2103-14 pubmed publisher..From these data we propose that selective age-related neuronal atrophy and neurodegeneration may be mediated by increased sortilin expression in neurons, together with elevated levels of proNGF expression in some targets. ..
- Al Shawi R, Hafner A, Chun S, Raza S, Crutcher K, Thrasivoulou C, et al. ProNGF, sortilin, and age-related neurodegeneration. Ann N Y Acad Sci. 2007;1119:208-15 pubmed..We therefore propose that increased proNGF in targets combined with increased sortilin expression in projecting neurons contributes to age-related neuronal atrophy and degeneration. ..
- Tominaga K, Kawahara T, Sano T, Toida K, Kuwano Y, Sasaki H, et al. Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach. Free Radic Biol Med. 2007;43:1627-38 pubmed..Thus, the Nox1-base oxidase may be a potential marker of neoplastic transformation and play an important role in oxygen radical- and inflammation-dependent carcinogenesis in the human stomach. ..
- Dergai M, Tsyba L, Dergai O, Zlatskii I, Skrypkina I, Kovalenko V, et al. Microexon-based regulation of ITSN1 and Src SH3 domains specificity relies on introduction of charged amino acids into the interaction interface. Biochem Biophys Res Commun. 2010;399:307-12 pubmed publisher..Thus microexons provide a mechanism for the control of tissue-specific interactions of ITSN1 and Src with their partners. ..
- Waibler Z, Anzaghe M, Ludwig H, Akira S, Weiss S, Sutter G, et al. Modified vaccinia virus Ankara induces Toll-like receptor-independent type I interferon responses. J Virol. 2007;81:12102-10 pubmed..These data provide the basis to further improve MVA as a vaccine vector. ..
- Bortolatto J, Borducchi E, Rodriguez D, Keller A, Faquim Mauro E, Bortoluci K, et al. Toll-like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin-specific allergic airway disease: role of MyD88 adaptor molecule and interleukin-12/interferon-gamma axis. Clin Exp Allergy. 2008;38:1668-79 pubmed publisher..Toll-like receptor 4 agonists co-adsorbed with allergen onto alum down-modulate allergic lung disease and prevent the development of polarized T cell-mediated airway inflammation. ..
- del Castillo F, Cohen Salmon M, Charollais A, Caille D, Lampe P, Chavrier P, et al. Consortin, a trans-Golgi network cargo receptor for the plasma membrane targeting and recycling of connexins. Hum Mol Genet. 2010;19:262-75 pubmed publisher..Sequence accession numbers. GenBank: Human CNST cDNA, NM_152609; mouse Cnst cDNA, NM_146105. ..
- Kubota N, Ebihara T, Matsumoto M, Gando S, Seya T. IL-6 and IFN-alpha from dsRNA-stimulated dendritic cells control expansion of regulatory T cells. Biochem Biophys Res Commun. 2010;391:1421-6 pubmed publisher..These data suggest that the balance of IL-6 and IFN-alpha in the region of RNA virus infection may determine the number of peripheral Treg, which affects the effective immune responses against viruses. ..
- N Diaye E, Hanyaloglu A, Kajihara K, Puthenveedu M, Wu P, von Zastrow M, et al. The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-coupled receptor endocytosis. Mol Biol Cell. 2008;19:1252-60 pubmed publisher..Identification of a negative regulator of GPCR clustering reveals a new function of ubiquitin-like proteins and highlights a cellular requirement for exquisite regulation of receptor dynamics. ..
- Calvisi D, Pinna F, Pellegrino R, Sanna V, Sini M, Daino L, et al. Ras-driven proliferation and apoptosis signaling during rat liver carcinogenesis is under genetic control. Int J Cancer. 2008;123:2057-64 pubmed publisher..Dusp1 possesses a prominent role in the acquisition of the phenotype resistant to HCC by BN rats, whereas late activation of RassF1A/Nore1A and Dab2IP/Ask1 axes is implicated in the highest apoptosis characteristic of BN HCC...
- Momboisse F, Ory S, Calco V, Malacombe M, Bader M, Gasman S. Calcium-regulated exocytosis in neuroendocrine cells: intersectin-1L stimulates actin polymerization and exocytosis by activating Cdc42. Ann N Y Acad Sci. 2009;1152:209-14 pubmed publisher..Here, we propose that the neuronal guanine nucleotide exchange factor, intersectin-1L, activates the GTPase Cdc42, which in turn provides de novo actin filaments that are important for calcium-regulated exocytosis in PC12 cells. ..
- Peng J, Yuan Q, Lin B, Panneerselvam P, Wang X, Luan X, et al. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. Eur J Immunol. 2010;40:1738-47 pubmed publisher..Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N-terminal and sterile alpha motif domains in the autoregulation of SARM activity. ..
- Scumpia P, Kelly Scumpia K, Delano M, Weinstein J, Cuenca A, Al Quran S, et al. Cutting edge: bacterial infection induces hematopoietic stem and progenitor cell expansion in the absence of TLR signaling. J Immunol. 2010;184:2247-51 pubmed publisher..Importantly, reduction in BM cellularity alone can reproduce HSPC expansion. These data show in vivo HSPC responses to bacterial infection are complex and not absolutely dependent upon key inflammatory signaling pathways...
- Uh A, Simmons C, Bresee C, Khoury N, Gombart A, Nicholson R, et al. MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line. Reprod Biol Endocrinol. 2009;7:74 pubmed publisher..MyD88 and TRIF exert direct regulatory effect on cAMP-induced CRH promoter activation in JEG3 cells in the absence of infection. MyD88 most likely interacts with molecules upstream of IRAK2 to regulate cAMP-induced CRH expression. ..
- Baird D, Stefan C, Audhya A, Weys S, Emr S. Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3. J Cell Biol. 2008;183:1061-74 pubmed publisher..Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches. We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling. ..
- Mari M, Bujny M, Zeuschner D, Geerts W, Griffith J, Petersen C, et al. SNX1 defines an early endosomal recycling exit for sortilin and mannose 6-phosphate receptors. Traffic. 2008;9:380-93 pubmed..Our data emphasize an important role of EEs in recycling to the TGN and indicate that different, specialized exit events occur on the same EE vacuole...
- Kopera I, Su L, Bilinska B, Cheng C, Mruk D. An in vivo study on adjudin and blood-testis barrier dynamics. Endocrinology. 2009;150:4724-33 pubmed publisher..Collectively these results demonstrate that adjudin targets the apical ES as well as the basal ES and tight junction, which in turn delays assembly of the BTB. ..
- Shen G, Whittington A, Song K, Wang P. Pleiotropic function of intersectin homologue Cin1 in Cryptococcus neoformans. Mol Microbiol. 2010;76:662-76 pubmed publisher..Our study presents the first evidence of a multi-modular protein whose function in intracellular transport underlies the growth, differentiation and virulence of a pathogenic microorganism. ..