F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse

Pérez‐Martínez, Manuel; Gordon-Alonso, Mónica; Cabrero, José Román; Barrero-Villar, Marta; Rey, Manuel; Mittelbrunn, Marı́a; Lamana, Amalia; Morlino, Giulia; Calabia, Carmen; Yamazaki, Hiroyuki; Shirao, Tomoaki; Vázquez, Jesús; González‐Amaro, Roberto; Veiga, Esteban; Sánchez-Madrid, Francisco

doi:10.1242/jcs.064238

Cited by 57 publications

(60 citation statements)

References 71 publications

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“…On the basis of the intracellular localization of DBN-1 and on a tentative functional comparison with its relatives, DBN-1 could furthermore modulate the plasticity and function of postsynaptic sites of neuromuscular junctions, analogous to mAbp1 and drebrin, which are known as essential players in both neurological [43][44][45]28 and immunological 30,29 synapses. In addition, DBN-1 may be involved in vesicle transport, similar to yeast and mammalian Abp1 homologues, which are well-described key regulators of receptor-mediated endocytosis, vesicle trafficking and endocytic structure disassembly [46][47][48][49]32 .…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, twinfilin binds to actin monomers and inhibits actin polymerization 25,26 . While the players of the third class, drebrin 1 (DBN1) and drebrin-like protein (DBNL; also known as Abp1, SH3P7 and HIP-55) have been associated with the function of neurological and immunological synapses [27][28][29][30] , their role in the sarcomere was unknown. Notably, in C2C12 myoblasts, expression of drebrin is induced during differentiation and is essential for myotube formation 31 .…”

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confidence: 99%

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Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction

et al. 2015

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Actin filament organization and stability in the sarcomeres of muscle cells are critical for force generation. Here we identify and functionally characterize a Caenorhabditis elegans drebrin-like protein DBN-1 as a novel constituent of the muscle contraction machinery. In vitro, DBN-1 exhibits actin filament binding and bundling activity. In vivo, DBN-1 is expressed in body wall muscles of C. elegans. During the muscle contraction cycle, DBN-1 alternates location between myosin-and actin-rich regions of the sarcomere. In contracted muscle, DBN-1 is accumulated at I-bands where it likely regulates proper spacing of a-actinin and tropomyosin and protects actin filaments from the interaction with ADF/cofilin. DBN-1 loss of function results in the partial depolymerization of F-actin during muscle contraction. Taken together, our data show that DBN-1 organizes the muscle contractile apparatus maintaining the spatial relationship between actin-binding proteins such as a-actinin, tropomyosin and ADF/cofilin and possibly strengthening actin filaments by bundling.

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Section: Discussionmentioning

confidence: 99%

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Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction

et al. 2015

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“…To assess the functional consequences of the effect of clathrin silencing on the physiology of the T cells, we measured the secretion of IL-2. It has been shown that reducing actin polymerization at the IS, either by using drugs, or by depleting actin-binding proteins, alters the secretion of IL-2 Perez-Martinez et al, 2010). Clathrin reduction deregulates IL-2 secretion (supplementary material Fig.…”

Section: Clathrin Is Necessary For Actin Accumulation At the Immunolomentioning

confidence: 99%

Endosomal clathrin drives actin accumulation at the immunological synapse

Calabia-Linares

Robles‐Valero

Fuente

et al. 2011

Journal of Cell Science

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SummaryAntigen-specific cognate interaction of T lymphocytes with antigen-presenting cells (APCs) drives major morphological and functional changes in T cells, including actin rearrangements at the immune synapse (IS) formed at the cell-cell contact area. Here we show, using cell lines as well as primary cells, that clathrin, a protein involved in endocytic processes, drives actin accumulation at the IS. Clathrin is recruited towards the IS with parallel kinetics to that of actin. Knockdown of clathrin prevents accumulation of actin and proteins involved in actin polymerization, such as dynamin-2, the Arp2/3 complex and CD2AP at the IS. The clathrin pool involved in actin accumulation at the IS is linked to multivesicular bodies that polarize to the cell-cell contact zone, but not to plasma membrane or Golgi complex. These data underscore the role of clathrin as a platform for the recruitment of proteins that promote actin polymerization at the interface of T cells and APCs.

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“…Drebrin is known to stabilize actin filaments (33,34). We have reported that the N-terminal region of drebrin associates with the cytoplasmic region of CXCR4 in CD4 ϩ T cells by three different approaches: mass spectrometry, pulldown assays, and co-immunoprecipitation (35). Despite containing a N-terminal ADF-H (actin depolymerizing factor homology) domain, drebrin only binds to polymerized (F-) actin and has no severing activity (36).…”

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confidence: 99%

“…Moreover, drebrin regulates the recruitment of other actin-regulatory proteins such as myosin, gelsolin, and profilin through direct association with them (38,39). We previously showed that interaction between drebrin and CXCR4 occurs at the T lymphocyte membrane and this molecular association is enhanced during superantigen presentation at the immunological synapse (35). However, the role of drebrin and its association with CXCR4 in controlling the cytoskeletal reorganization triggered by HIV-1 infection has not been previously described.…”

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confidence: 99%

Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection

Gordon-Alonso

Rocha-Perugini

Álvarez

et al. 2013

Journal of Biological Chemistry

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Background: Drebrin binds to F-actin and CXCR4 in T cells. Thus, it is a potential candidate for the modulation of HIV-1 infection. Results: Drebrin and CXCR4 accumulate at viral attachment areas. Drebrin knockdown decreases F-actin polymerization, and increases local profilin accumulation and HIV-1 infection. Conclusion: Drebrin inhibits HIV-1 entry by stabilizing HIV-1-triggered F-actin polymerization. Significance: Modulation of actin dynamics differentially regulates each viral step for an effective viral infection. HIV-1 contact with target cells triggers F-actin rearrangements that are essential for several steps of the viral cycle. Successful HIV entry into CD4؉ T cells requires actin reorganization induced by the interaction of the cellular receptor/co-receptor complex CD4/CXCR4 with the viral envelope complex gp120/gp41 (Env).In this report, we analyze the role of the actin modulator drebrin in HIV-1 viral infection and cell to cell fusion. We show that drebrin associates with CXCR4 before and during HIV infection. Drebrin is actively recruited toward cellvirus and Env-driven cell to cell contacts. After viral internalization, drebrin clustering is retained in a fraction of the internalized particles. Through a combination of RNAi-based inhibition of endogenous drebrin and GFP-tagged expression of wild-type and mutant forms, we establish drebrin as a negative regulator of HIV entry and HIV-mediated cell fusion. Down-regulation of drebrin expression promotes HIV-1 entry, decreases F-actin polymerization, and enhances profilin local accumulation in response to HIV-1. These data underscore the negative role of drebrin in HIV infection by modulating viral entry, mainly through the control of actin cytoskeleton polymerization in response to HIV-1.Human immunodeficiency virus (HIV)-1 entry requires fusion between the viral envelope and the plasma membrane of the target cell (1). This process is mediated by the viral envelope glycoprotein complex gp120/gp41 (Env), 5 which interacts first with CD4 and then with a co-receptor, one of the chemokine receptors CCR5 or CXCR4 (2, 3).For the viral and cellular membranes to fuse, a critical number of gp120-CD4/coreceptor engagements are needed to establish an energetically productive fusion pore (4). HIV-1 can also be transmitted from infected to uninfected cells through cell to cell contacts, called virological synapses because of their similarities to the immunological synapse (5). As an example, CD4 and CXCR4 recruitment (6 -8) and local actin polymerization take place in both processes (6, 9 -11). Receptor clustering is regulated by two main factors: 1) insertion into specific membrane domains by lateral membrane receptor interactions (12) such as lipid rafts (13) or tetraspanin-enriched microdomains (14 -17); and 2) actin remodeling (6, 18 -20). This phenomenon is well illustrated by experiments in which HIV-1 contact induces CD4 and CXCR4 capping at the plasma membrane of target CD4 ϩ T lymphocytes (21,22). Receptor capping requires the formation of a subcortical...

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F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse

Cited by 57 publications

References 71 publications

Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction

Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction

Endosomal clathrin drives actin accumulation at the immunological synapse

Actin-binding Protein Drebrin Regulates HIV-1-triggered Actin Polymerization and Viral Infection

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