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PubMed1994

Drug trafficking among African-American early adolescents: prevalence, consequences, and associated behaviors and beliefs.

OBJECTIVE/METHODOLOGY: Drug trafficking by minority youths in low-income, urban areas has received considerable publicity from the mass media in the past half-decade. However, there has been corresponding little exposition of this problem in the medical literature. This review was undertaken to provide an overview of the epidemiology and consequences of drug trafficking among urban youths and to describe factors associated with drug trafficking. RESULTS: Existing data indicate that approximately 10% of male, urban, African-American early adolescents report having engaged in drug trafficking, with a higher percent of youths reporting having been asked to sell drugs and/or indicating that they expect to become involved in drug trafficking. Rates increase with advancing age. Reported rates of drug trafficking are comparable with rates of tobacco and alcohol use among early adolescents and are substantially higher than use rates of illegal drugs. Drug trafficking is associated with increased mortality, accounting for one third to one half of homicide-related deaths in some studies. The practice is also associated with other health-risk behaviors, including nonfatal violence, substance use, and incarceration. Perceived social pressures by family members and/or peers to engage in drug trafficking and the belief that a youth's wage-earning potential is limited to drug trafficking are highly correlated with involvement in this activity. CONCLUSIONS: Drug trafficking is a prevalent risk behavior among adolescents that has several negative health consequences.

Adolescent↗

PubMed2002

ADP-ribosylation factor 1 of Arabidopsis plays a critical role in intracellular trafficking and maintenance of endoplasmic reticulum morphology in Arabidopsis.

ADP-ribosylation factors (Arf), a family of small GTP-binding proteins, play important roles in intracellular trafficking in animal and yeast cells. Here, we investigated the roles of two Arf homologs, Arf1 and Arf3 of Arabidopsis, in intracellular trafficking in plant cells. We generated dominant negative mutant forms of Arf 1 and Arf3 and examined their effect on trafficking of reporter proteins in protoplasts. Arf1[T31N] inhibited trafficking of H(+)-ATPase:green fluorescent protein (GFP) and sialyltransferase (ST):GFP to the plasma membrane and the Golgi apparatus. In addition, Arf1[T31N] caused relocalization of the Golgi reporter protein ST:GFP to the endoplasmic reticulum (ER). In protoplasts expressing Arf1[T31N], ST:red fluorescent protein remained in the ER, whereas H(+)-ATPase:GFP was mistargeted to another organelle. Also, expression of Arf1[T31N] in protoplasts resulted in profound changes in the morphology of the ER. The treatment of protoplasts with brefeldin A had exactly the same effect as Arf1[T31N] on various intracellular trafficking pathways. In contrast, Arf3[T31N] did not affect trafficking of any of these reporter proteins. Inhibition experiments using mutants with various domains swapped between Arf1 and Arf3 revealed that the N-terminal domain is interchangeable for trafficking inhibition. However, in addition to the T31N mutation, motifs in domains II, III, and IV of Arf1 were necessary for inhibition of trafficking of H(+)-ATPase:GFP. Together, these results strongly suggest that Arf1 plays a role in the intracellular trafficking of cargo proteins in Arabidopsis, and that Arf1 functions through a brefeldin A-sensitive factor.

ADP-Ribosylation Factor 1↗

PubMed1999

Exposure to drug trafficking among urban, low-income African American children and adolescents.

OBJECTIVE: To examine the association between exposure to drug trafficking (selling or delivering drugs) and exposure to other forms of community violence and risk behaviors among urban, low-income African American children and adolescents. DESIGN: Community-based, cross-sectional survey. SETTING: Ten public housing developments in a large eastern city in the United States. PARTICIPANTS: Three hundred forty-nine urban, low-income African American children and adolescents (198 boys and 151 girls), aged 9 to 15 years. MAIN OUTCOME MEASURES: Exposure to drug trafficking and other forms of community violence (as either a victim or a witness), risk behaviors/perceptions including risk-taking/delinquency, drug use, perpetration of violence or other crimes, threats to school achievement, and perceived peer involvement. ANALYSIS: Exploratory factor analysis was performed to examine whether exposure to drug trafficking is a risk factor that is distinct from other exposure to violence. Multivariate analysis of variance and chi2 tests were performed to assess the relationship between exposure to drug trafficking and other forms of community violence and risk behaviors/perceptions. RESULTS: Of 349 participants, 63 (18%) had been asked to traffic drugs and 134 (38%) had seen someone else being asked to traffic drugs. Factor analysis indicates that exposure to drug trafficking appears to be different from other forms of community violence. However, having been asked and having seen other people being asked to traffic drugs were both strongly associated with exposure to other forms of community violence. Compared with children and adolescents who had not been exposed to drug trafficking, those who were exposed to drug trafficking reported more risk-taking and delinquent behaviors, drug use, threats to achievement, and a perception of more peer involvement in these risk behaviors. CONCLUSION: Exposure to drug trafficking is a unique risk factor that is strongly associated with exposure to other forms of community violence and involvement in other risk behaviors.

Adolescent↗

PubMed2004

Direct role of a viroid RNA motif in mediating directional RNA trafficking across a specific cellular boundary.

The plasmodesmata and phloem form a symplasmic network that mediates direct cell-cell communication and transport throughout a plant. Selected endogenous RNAs, viral RNAs, and viroids traffic between specific cells or organs via this network. Whether an RNA itself has structural motifs to potentiate trafficking is not well understood. We have used mutational analysis to identify a motif that the noncoding Potato spindle tuber viroid RNA evolved to potentiate its efficient trafficking from the bundle sheath into mesophyll that is vital to establishing systemic infection in tobacco (Nicotiana tabacum). Surprisingly, this motif is not necessary for trafficking in the reverse direction (i.e., from the mesophyll to bundle sheath). It is not required for trafficking between other cell types either. We also found that the requirement for this motif to mediate bundle sheath-to-mesophyll trafficking is dependent on leaf developmental stages. Our results provide genetic evidence that (1) RNA structural motifs can play a direct role in mediating trafficking across a cellular boundary in a defined direction, (2) the bundle sheath-mesophyll boundary serves as a novel regulatory point for RNA trafficking between the phloem and nonvascular tissues, and (3) the symplasmic network remodels its capacity to traffic RNAs during plant development. These findings may help further studies to elucidate the interactions between RNA motifs and cellular factors that potentiate directional trafficking across specific cellular boundaries.

Base Sequence↗

PubMed2005

Actin filaments play a critical role in vacuolar trafficking at the Golgi complex in plant cells.

Actin filaments are thought to play an important role in intracellular trafficking in various eukaryotic cells. However, their involvement in intracellular trafficking in plant cells has not been clearly demonstrated. Here, we investigated the roles actin filaments play in intracellular trafficking in plant cells using latrunculin B (Lat B), an inhibitor of actin filament assembly, or actin mutants that disrupt actin filaments when overexpressed. Lat B and actin2 mutant overexpression inhibited the trafficking of two vacuolar reporter proteins, sporamin:green fluorescent protein (GFP) and Arabidopsis thaliana aleurain-like protein:GFP, to the central vacuole; instead, a punctate staining pattern was observed. Colocalization experiments with various marker proteins indicated that these punctate stains corresponded to the Golgi complex. The A. thaliana vacuolar sorting receptor VSR-At, which mainly localizes to the prevacuolar compartment, also accumulated at the Golgi complex in the presence of Lat B. However, Lat B had no effect on the endoplasmic reticulum (ER) to Golgi trafficking of sialyltransferase or retrograde Golgi to ER trafficking. Lat B also failed to influence the Golgi to plasma membrane trafficking of H+-ATPase:GFP or the secretion of invertase:GFP. Based on these observations, we propose that actin filaments play a critical role in the trafficking of proteins from the Golgi complex to the central vacuole.

Actins↗

PubMed2006

Subcellular trafficking of the Arabidopsis auxin influx carrier AUX1 uses a novel pathway distinct from PIN1.

The directional flow of the plant hormone auxin mediates multiple developmental processes, including patterning and tropisms. Apical and basal plasma membrane localization of AUXIN-RESISTANT1 (AUX1) and PIN-FORMED1 (PIN1) auxin transport components underpins the directionality of intercellular auxin flow in Arabidopsis thaliana roots. Here, we examined the mechanism of polar trafficking of AUX1. Real-time live cell analysis along with subcellular markers revealed that AUX1 resides at the apical plasma membrane of protophloem cells and at highly dynamic subpopulations of Golgi apparatus and endosomes in all cell types. Plasma membrane and intracellular pools of AUX1 are interconnected by actin-dependent constitutive trafficking, which is not sensitive to the vesicle trafficking inhibitor brefeldin A. AUX1 subcellular dynamics are not influenced by the auxin influx inhibitor NOA but are blocked by the auxin efflux inhibitors TIBA and PBA. Furthermore, auxin transport inhibitors and interference with the sterol composition of membranes disrupt polar AUX1 distribution at the plasma membrane. Compared with PIN1 trafficking, AUX1 dynamics display different sensitivities to trafficking inhibitors and are independent of the endosomal trafficking regulator ARF GEF GNOM. Hence, AUX1 uses a novel trafficking pathway in plants that is distinct from PIN trafficking, providing an additional mechanism for the fine regulation of auxin transport.

Actins↗

PubMed1994

Recent and intended drug trafficking among male and female urban African-American early adolescents.

OBJECTIVE: To investigate associations between recent and intended involvement in drug trafficking and perceptions of the social environment among high-risk urban African-American youths. METHODS: A multicomponent risk assessment survey was conducted among a convenience sample of 351 African-American youths 9 through 15 years of age residing in low-income communities. Both univariate analysis and logistic regression were performed to examine the association of youths' perceived social environment with recent and intended involvement in drug trafficking. RESULTS: Drug selling or delivering in the previous 6 months was reported by 6% of the youths; 12% expected to engage in these activities in the next 6 months. There was a strong association between drug trafficking and other high-risk behaviors, including drug use. Among both genders, perceptions that neighbors, friends, or family members were involved in drug trafficking were correlated with recent or intended drug trafficking. For boys, personal economic needs had a strong association with drug trafficking. For girls, personal feelings were more important correlates of intended involvement. CONCLUSIONS: Efforts aimed at both drug-trafficking prevention and intervention need to be community-based and multifaceted. Programs should address the youths' perceived social environments and consider gender differences regarding correlates of drug-trafficking involvement.

Adolescent↗

PubMed2005

Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells.

Feline brain endothelial cells (BECs), astrocytes, and microglia were combined in different configurations in a cell culture insert system to assess the effect of different cell types on the trafficking of peripheral blood mononuclear cell (PBMC) subsets in response to feline immunodeficiency virus (FIV). The addition of astrocytes to BECs significantly increased the adherence of PBMCs. This increase in adherence was suppressed by microglia, whereas microglia alone had no effect on PBMC adherence. FIV exposure of the glial cells did not alter PBMC adherence as compared to same configurations with untreated cells. All PBMC subsets showed some level of trafficking across the endothelial cell layer. The level of trafficking of monocytes and B cells was significantly increased if astrocytes were present. The presence of microglia with the astrocytes reduced transmigration across all PBMC subsets. FIV exposure of astrocytes significantly increased the percentage of CD8 T cell transmigration from 24% to 64% of the total CD4 and CD8 numbers. The presence of microglia significantly reversed the preferential trafficking of CD8 cells in the presence of astrocytes. The results suggested that interaction between the triad of endothelial cells, astrocytes, and microglia played an important, but varying, role in the trafficking of different PBMC subsets. In general, astrocytes had a positive effect on trafficking of PBMCs, while microglia had a suppressive effect. Effects of FIV on trafficking were largely restricted to increases seen in CD8 T cells and monocytes.

Animals↗

PubMed2006

Dorsal-ventral pattern of Delta trafficking is established by a Snail-Tom-Neuralized pathway.

The intracellular trafficking of the Notch ligand Delta plays an important role in the activation of the Notch pathway. We have addressed the snail-dependent regulation of Delta trafficking during the plasma membrane growth of the mesoderm in the Drosophila embryo. We show that Delta is retained in endocytic vesicles in the mesoderm but expressed on the surface of the adjacent ectoderm. This trafficking pattern requires Neuralized. We developed a protocol based on chromosomal deletion and microarray analysis that led to the identification of tom as the target of snail regulating Delta trafficking. Snail represses Tom expression in the mesoderm and thereby activates Delta trafficking. Overexpression of Tom abolishes Delta trafficking and signaling to the adjacent mesoectoderm. Loss of Tom produces mesoderm-type Delta trafficking in the entire blastoderm epithelium and an expansion of mesoectoderm gene expression. We propose that Tom antagonizes the activity of Neuralized and thus establishes a sharp mesoderm-mesoectoderm boundary of Notch signaling.

Animals↗

PubMed2003

Endocytic trafficking during Drosophila development.

During the last decade, many of the factors and mechanisms controlling membrane and protein trafficking in general and endocytic trafficking in particular have been uncovered. We have a detailed understanding of the different endocytic trafficking steps: plasma membrane budding, endocytic vesicle motility and fusion with the endosome, recycling, transcytosis and lysosomal degradation. The kinetics and trafficking pathway of many signaling receptors and the relevance of endocytic trafficking during signaling in many mammalian cultured cells are also well understood. However, only in recent years has the role of endocytic trafficking during cell-to-cell communication during development, i.e. during patterning, induction and lateral inhibition, begun to be explored. The contribution of Drosophila developmental genetics and cell biology has been fundamental in elucidating the essential role of endocytosis during these processes. Reviewed here are some of the recent developments on the role of endocytic trafficking during long- and short-range signaling and during lateral inhibition.

Animals↗

PubMed2004

Knowledge, attitudes and experiences of sex trafficking by young women in Benin City, South-South Nigeria.

Benin City, the headquarters of Edo State, is known to have one of the highest rates of international sex trafficking of young women in Nigeria. This study was designed to determine the knowledge, attitudes and experiences of young women in Benin City, towards international sex trafficking. A random household sample of 1456 women aged 15-25 years was interviewed with a structured questionnaire that elicited information on women's experiences of, and attitudes towards international sex trafficking. The results indicate that 97.4% of the women have heard of international sex trafficking; 70% had female relatives who lived in the receiving countries of Italy, Spain, and the Netherlands; while 44.0% knew of someone who was currently engaged in sex work abroad. Up to 32% of the women reported that they had been approached by someone offering to assist them to travel abroad. Women of poorer socio-economic status (being out-of-school, unemployed, parents uneducated and unemployed) were more likely to report having been offered assistance to travel abroad. Up to 81.5% of the women supported the notion that sex trafficking should be stopped, while 18.5% felt it should be allowed to continue. The perception that sex trafficking leads to wealth creation and economic gains for women was the most common reason proffered by those wanting the practice to continue. By contrast, the fear of adverse health consequences and the need to maintain social and religious morals were the reasons given by those wanting the practice to discontinue. These results suggest that programs that promote the economic well being of women, and social advocacy focusing on harm reduction will be most helpful in reducing the rate of sex trafficking in Benin City.

Adolescent↗

PubMed2002

Regulation of protein and vesicle trafficking at the apical membrane of epithelial cells.

The characterization of endocytotic and post-endocytotic trafficking pathways at the apical membrane of epithelial cells presents a potential avenue for the identification of targets to modulate the initial stages of absorption and transepithelial transport of macromolecules. In addition, it is becoming increasingly clear that the activity of a number of apical membrane transporters is acutely regulated by vesicular trafficking. The gastric HCl-secreting parietal (oxyntic) cell is a model system to characterize an apical membrane vesicular trafficking pathway and its relationship to the regulation of the function of the gastric proton pump. The subapical tubulovesicular compartment of the parietal cell is highly enriched in the H,K-ATPase and is a key endosomal-like system in the apical membrane recycling pathway. In the process of cataloging the proteins that interact with the H,K-ATPase and tubulovesicles, we have identified novel components that may regulate protein sorting through this compartment and candidate linker proteins between the vesicular trafficking machinery and the cytoskeleton. One protein associated with H,K-ATPase-rich tubulovesicles is the nonreceptor tyrosine kinase c-src, identified by a screen for dynamin-binding proteins. The tyrosine kinase is active, as it can tyrosine-phosphorylate tubulovesicular proteins in vitro. One of the tyrosine-phosphorylated proteins of M(r) 100 kDa may be the H,K-ATPase itself, or a protein in a complex with the H,K-ATPase that is stable to dissociation by nonionic detergents. By virtue of its association with tubulovesicular membranes, c-src may regulate the trafficking and/or activity of the H,K-ATPase. A second protein identified by a screen for dynamin-binding proteins is the protein lasp-1. Lasp-1, through its modular protein structure, may bind to dynamin and to the actin cytoskeleton, thus linking the vesicular trafficking machinery with the cytoskeleton. These two examples illustrate the utility of the parietal cell in the biochemical characterization of components potentially involved in the regulation of apical membrane trafficking pathways.

Animals↗

PubMed2004

Intracellular trafficking of the human Wilson protein: the role of the six N-terminal metal-binding sites.

The Wilson protein (ATP7B) is a copper-transporting CPx-type ATPase defective in the copper toxicity disorder Wilson disease. In hepatocytes, ATP7B delivers copper to apo-ceruloplasmin and mediates the excretion of excess copper into bile. These distinct functions require the protein to localize at two different subcellular compartments. At the trans-Golgi network, ATP7B transports copper for incorporation into apo-ceruloplasmin. When intracellular copper levels are increased, ATP7B traffics to post-Golgi vesicles in close proximity to the canalicular membrane to facilitate biliary copper excretion. In the present study, we investigated the role of the six N-terminal MBSs (metal-binding sites) in the trafficking process. Using site-directed mutagenesis, we mutated or deleted various combinations of the MBSs and assessed the effect of these changes on the localization and trafficking of ATP7B. Results show that the MBSs required for trafficking are the same as those previously found essential for the copper transport function. Either MBS 5 or MBS 6 alone was sufficient to support the redistribution of ATP7B to vesicular compartments. The first three N-terminal motifs were not required for copper-dependent intracellular trafficking and could not functionally replace sites 4-6 when placed in the same sequence position. Furthermore, the N-terminal region encompassing MBSs 1-5 (amino acids 64-540) was not essential for trafficking, with only one MBS close to the membrane channel, necessary and sufficient to support trafficking. Our findings were similar to those obtained for the closely related ATP7A protein, suggesting similar mechanisms for trafficking between copper-transporting CPx-type ATPases.

Adenosine Triphosphatases↗

PubMed2006

Longin-like folds identified in CHiPS and DUF254 proteins: vesicle trafficking complexes conserved in eukaryotic evolution.

Eukaryotic protein trafficking pathways require specific transfer of cargo vesicles to different target organelles. A number of vesicle trafficking and membrane fusion components participate in this process, including various tethering factor complexes that interact with small GTPases prior to SNARE-mediated vesicle fusion. In Saccharomyces cerevisiae a protein complex of Mon1 and Ccz1 functions with the small GTPase Ypt7 to mediate vesicle trafficking to the vacuole. Mon1 belongs to DUF254 found in a diverse range of eukaryotic genomes, while Ccz1 includes a CHiPS domain that is also present in a known human protein trafficking disorder gene (HPS-4). The present work identifies the CHiPS domain and a sequence region from another trafficking disorder gene (HPS-1) as homologs of an N-terminal domain from DUF254. This link establishes the evolutionary conservation of a protein complex (HPS-1/HPS-4) that functions similarly to Mon1/Ccz1 in vesicle trafficking to lysosome-related organelles of diverse eukaryotic species. Furthermore, the newly identified DUF254 domain is a distant homolog of the mu-adaptin longin domain found in clathrin adapter protein (AP) complexes of known structure that function to localize cargo protein to specific organelles. In support of this fold assignment, known longin domains such as the AP complex sigma-adaptin, the synaptobrevin N-terminal domains sec22 and Ykt6, and the srx domain of the signal recognition particle receptor also regulate vesicle trafficking pathways by mediating SNARE fusion, recognizing specialized compartments, and interacting with small GTPases that resemble Ypt7.

Amino Acid Sequence↗

PubMed2001

RNA trafficking signals in human immunodeficiency virus type 1.

Intracellular trafficking of retroviral RNAs is a potential mechanism to target viral gene expression to specific regions of infected cells. Here we show that the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized extensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2 dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the same RNA trafficking granules and are cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in targeting HIV gene expression is discussed.

Animals↗

PubMed2003

Developmental regulation and significance of KNOX protein trafficking in Arabidopsis.

Intercellular communication delivers critical information for position-dependent specification of cell fate. In plants, a novel mechanism for cell-to-cell communication involves the intercellular trafficking of regulatory proteins and mRNAs. The maize KNOTTED1 (KN1) gene acts non cell-autonomously in the maize leaf, and KN1 was the first plant protein shown to traffic cell-to-cell, presumably through plasmodesmata. We have compared the intercellular trafficking of green fluorescent protein (GFP) fusions of KN1 and Arabidopsis KN1-related homeobox proteins to that of the viral movement protein from turnip vein clearing tobamovirus. We show that there is specific developmental regulation of GFP approximately KN1 trafficking. GFP -- KN1 was able to traffic from the inner layers of the leaf to the epidermis, but not in the opposite direction, from epidermis to mesophyll. However, GFP or the GFP -- movement protein fusion moved readily out of the epidermis. GFP -- KN1 was however able to traffic out of the epidermal (L1) layer in the shoot apical meristem, indicating that KN1 movement out of the L1 was developmentally regulated. GFP -- KNAT1/BREVIPEDICELLUS and GFP -- SHOOTMERISTEMLESS fusions could also traffic from the L1 to the L2/L3 layers of the meristem. In a test for the functional significance of trafficking, we showed that L1-specific expression of KN1 or of KNAT1 was able to partially complement the strong shootmeristemless-11 (stm-11) mutant. However, a cell-autonomous GUS fusion to KN1 showed neither trafficking ability nor complementation of stm-11 when expressed in the L1. These results suggest that the activity of KN1 and related homeobox proteins is maintained following intercellular trafficking, and that trafficking may be required for their normal developmental function.

Arabidopsis↗

PubMed2006

State-dependent AMPA receptor trafficking in the mammalian retina.

The rapid cycling of AMPA receptors (AMPARs) at the membrane maintains synaptic transmission at a number of CNS synapses and may play a role in several forms of synaptic plasticity. It is unclear, however, how prevalent the trafficking of AMPARs is in the CNS, particularly at synapses not known to exhibit activity-dependent plasticity. Because trafficking is regulated by basal synaptic activity, a question also remains as to how receptor trafficking is modulated at synapses subject to different patterns of synaptic activation. We have investigated whether trafficking of AMPARs occurs in retinal neurons, which are subject to tonic glutamate release. We find two distinct states of AMPAR trafficking in ON ganglion cells. Light adaptation serves to stabilize AMPARs in a noncycling mode. However, dark adaptation for as little as 8 h triggers a switch to a second state of trafficking characterized by rapid cycling. We provide evidence that the activation of AMPARs is critical for switching between cycling and noncycling states. The induction of cycling further appears to be modulated by changes in the function of glutamate receptor 2/3-interacting proteins. Our results suggest that there is a strong link between synaptic activity and AMPAR trafficking in retinal neurons. These results further suggest the existence of a previously unknown form of activity-dependent plasticity in the retina that may be regulated in the course of a normal light/dark cycle.

Animals↗

PubMed2006

Protein kinase Balpha is required for vesicle trafficking and class II presentation of IgA Fc receptor (CD89)-targeted antigen.

Ag presentation stimulates Ag-specific adaptive immune responses. FcalphaR (CD89)-mediated capture of IgA-bound exogenous Ag leads to efficient MHC class II Ag presentation by APCs. CD89 signaling is required for trafficking of internalized Ag to specialized multivesicular bodies known as MHC class II compartments (MIIC) and subsequent class II presentation. In the present study, we tested the hypothesis that the vesicle trafficking regulator protein kinase Balpha (PKBalpha) is required for CD89-mediated trafficking to MIIC and Ag presentation. We observed by two independent methods (chemical inhibitors and specific RNA interference) that PKBalpha was required for CD89 trafficking to MIIC and class II Ag presentation. Expression of constitutively active PKBalpha in APCs expressing a mutant CD89 accessory signaling molecule (deficient in CD89/Ag trafficking, processing, and presentation) induced trafficking of CD89 to lamp1-containing late endocytic vesicles, but not class II-containing vesicles (MIIC), or class II Ag presentation. These studies show for the first time that PKBalpha is required for receptor-mediated Ag presentation and suggest the mechanism of action includes regulation of vesicle trafficking.

Antigen Presentation↗