The Actin Cytoskeleton is Required for the Trafficking of the B Cell Antigen Receptor to the Late Endosomes

Brown, Bruce K.; Song, Wenxia

doi:10.1034/j.1600-0854.2001.002006414.x

Cited by 80 publications

(102 citation statements)

References 59 publications

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“…In this study, we found that the increase in BCR residency in the surface-signaling microdomains and BCR-triggered protein phosphorylation was associated with a decrease in BCR internalization. This is consistent with our previous observation that an inhibition of BCR internalization slowed down the attenuation of BCR-triggered protein tyrosine phosphorylation (34). These results suggest that inhibition of internalization is one of the mechanisms for stabilizing surface-signaling microdomains.…”

Section: Discussionsupporting

confidence: 82%

“…The surface BCR of CH27 and splenic B cells was labeled with Cy3-conjugated Fab of goat anti-mouse IgM Ab (Cy3-Fab anti-IgM) at 4°C in the presence or absence of either 20 g/ml B-anti-Ig or 20 g/ml B-anti-Ig plus 20 g/ml avidin. As previously shown, B-anti-Ig does not compete with Fab-anti-IgM to bind to the BCR (5,34). After incubation at 37°C for 60 min, cells were cooled to 4°C and incubated with FITC-CTX without permeabilization to label the surface G M1 .…”

Section: Ag Valency and The Formation Of Bcr-signaling Microdomainsmentioning

confidence: 99%

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Polyvalent Antigens Stabilize B Cell Antigen Receptor Surface Signaling Microdomains

Thyagarajan

Arunkumar

Song

2003

The Journal of Immunology

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The B cell Ag receptor (BCR) can distinguish subtle differences in Ag structure and trigger differential responses. In this study, we analyzed the effects of Ag valency on the signaling and Ag-targeting functions of the BCR. Although both paucivalent and polyvalent Ags induced the redistribution of the surface BCR into polarized caps, polyvalent Ag-induced BCR caps persisted. Ganglioside GM1, a lipid raft marker, and tyrosine-phosphorylated proteins, but not CD45 and transferrin receptor, were concentrated in BCR caps, suggesting BCR caps as surface-signaling microdomains. Prolonged BCR caps were concomitant with an increase in the level and duration of protein tyrosine phosphorylation and a reduction in BCR internalization and movement to late endosomes/lysosomes. Thus, Ag valency influences B cell responses by modulating the stability of BCR-signaling microdomains and BCR trafficking.

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Section: Discussionsupporting

confidence: 82%

Section: Ag Valency and The Formation Of Bcr-signaling Microdomainsmentioning

confidence: 99%

Polyvalent Antigens Stabilize B Cell Antigen Receptor Surface Signaling Microdomains

Thyagarajan

Arunkumar

Song

2003

The Journal of Immunology

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“…BCR activation induces reorganization of the actin cytoskeleton (24,25). The presence of two ABDs in Abp1 implies that its cellular redistribution may rely on BCR-induced actin cytoskeleton reorganization.…”

Section: Bcr-induced Abp1 Redistribution Depends On the Actin Cytoskementioning

confidence: 99%

“…We previously demonstrated that the dynamic property of the actin cytoskeleton was required for signal-stimulated BCR internalization. BCR endocytosis is blocked at the pinching-off step during clathrin-coated vesicle formation in the absence of the functional actin cytoskeleton (24). Stoddart et al (26) suggested an actin cytoskeleton-dependent and clathrin-independent BCR internalization pathway in DT40 chicken B cells.…”

mentioning

confidence: 99%

“…Early studies showed that Ag binding induced the translocation of the BCR and tyrosine kinases Lyn and Syk to the detergent-insoluble cytoskeletal fractions (16 -18), reorganization of the actin cytoskeleton (19 -23), and transient increases in F-actin levels in B cells (24,25). Hao and August (25) recently showed that disruption of the actin cytoskeleton altered BCR-induced activation of the MAPK ERK and transcription factors serum response factor, NF-AT, and NF-B.…”

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Actin-Binding Protein 1 Regulates B Cell Receptor-Mediated Antigen Processing and Presentation in Response to B Cell Receptor Activation

Onabajo

Seeley

Kale

et al. 2008

The Journal of Immunology

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The BCR serves as both signal transducer and Ag transporter. Binding of Ags to the BCR induces signaling cascades and Ag processing and presentation, two essential cellular events for B cell activation. BCR-initiated signaling increases BCR-mediated Ag-processing efficiency by increasing the rate and specificity of Ag transport. Previous studies showed a critical role for the actin cytoskeleton in these two processes. In this study, we found that actin-binding protein 1 (Abp1/HIP-55/SH3P7) functioned as an actin-binding adaptor protein, coupling BCR signaling and Ag-processing pathways with the actin cytoskeleton. Gene knockout of Abp1 and overexpression of the Src homology 3 domain of Abp1 inhibited BCR-mediated Ag internalization, consequently reducing the rate of Ag transport to processing compartments and the efficiency of BCR-mediated Ag processing and presentation. BCR activation induced tyrosine phosphorylation of Abp1 and translocation of both Abp1 and dynamin 2 from the cytoplasm to plasma membrane, where they colocalized with the BCR and cortical F-actin. Mutations of the two tyrosine phosphorylation sites of Abp1 and depolymerization of the actin cytoskeleton interfered with BCR-induced Abp1 recruitment to the plasma membrane. The inhibitory effect of a dynamin proline-rich domain deletion mutant on the recruitment of Abp1 to the plasma membrane, coimmunoprecipitation of dynamin with Abp1, and coprecipitation of Abp1 with GST fusion of the dyanmin proline-rich domain demonstrate the interaction of Abp1 with dynamin 2. These results demonstrate that the BCR regulates the function of Abp1 by inducing Abp1 phosphorylation and actin cytoskeleton rearrangement, and that Abp1 facilitates BCR-mediated Ag processing by simultaneously interacting with dynamin and the actin cytoskeleton.

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Functional and structural requirements for the internalization of distinct BCR‐ligand complexes

et al. 2006

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Antigen (Ag) binding to the BCR rapidly initiates two important events: a phosphorylation cascade that results in the production of secondary signaling intermediaries and the internalization of Ag-BCR complexes. Previous studies using anti-BCR antibodies (Ab) have suggested that BCR signaling is an essential requirement for BCR endocytosis and have further implicated lipid rafts as essential platforms for both BCR functions. However, published data from our laboratory indicate that lipid rafts and consequently raft-mediated signaling are dispensable for BCR-mediated internalization of Ag-specific BCR. Therefore, we investigated the relationship between BCR signaling and endocytosis by defining the role of early kinase signaling in the BCRmediated internalization of a model Ag (haptenated protein). The results demonstrate that Src kinases and Syk-mediated BCR signaling are not essential for BCR-mediated Ag internalization. Moreover, by comparing Ag and Ab, it was determined that while both localize to clathrin-coated pits, the internalization of Ab-BCR complexes is more susceptible to inhibition of signaling and highly sensitive to disruption of lipid rafts and the actin cytoskeleton compared to Ag-BCR complexes. Thus, these results demonstrate that the nature of the ligand ultimately determines the functional requirements and relative contribution of lipid rafts and other membrane structures to the internalization of BCR-ligand complexes.

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The Actin Cytoskeleton is Required for the Trafficking of the B Cell Antigen Receptor to the Late Endosomes

Cited by 80 publications

References 59 publications

Polyvalent Antigens Stabilize B Cell Antigen Receptor Surface Signaling Microdomains

Polyvalent Antigens Stabilize B Cell Antigen Receptor Surface Signaling Microdomains

Actin-Binding Protein 1 Regulates B Cell Receptor-Mediated Antigen Processing and Presentation in Response to B Cell Receptor Activation

Functional and structural requirements for the internalization of distinct BCR‐ligand complexes

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