Rab35 Controls Actin Bundling by Recruiting Fascin as an Effector Protein

Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (Impact Factor: 33.61). 10/2009; 325(5945):1250-4. DOI: 10.1126/science.1174921
Source: PubMed


Actin filaments are key components of the eukaryotic cytoskeleton that provide mechanical structure and generate forces during cell shape changes, growth, and migration. Actin filaments are dynamically assembled into higher-order structures at specified locations to regulate diverse functions. The Rab family of small guanosine triphosphatases is evolutionarily conserved and mediates intracellular vesicle trafficking. We found that Rab35 regulates the assembly of actin filaments during bristle development in Drosophila and filopodia formation in cultured cells. These effects were mediated by the actin-bundling protein fascin, which directly associated with active Rab35. Targeting Rab35 to the outer mitochondrial membrane triggered actin recruitment, demonstrating a role for an intracellular trafficking protein in localized actin assembly.

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    • "The other Rab35 effector is centaurin-b2, an Arf6 GAP, which inactivates Arf6 (Kobayashi and Fukuda 2012), a step required for EHD1 recruitment to Arf6-positive endosomes. Like Rab8 and Rab11, Rab35 is able to control membrane transport and actin dynamics, activating Cdc42 through a yet-unknown mechanism (Chevallier et al. 2009) and inducing filopodia protrusion through fascin, a Cdc42 downstream effector (Zhang et al. 2009). This dual role of Rab35 makes it an interesting candidate to regulate a possible crosstalk between trafficking and cytoskeleton dynamics during neurite elongation. "
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    ABSTRACT: Neuronal cells are characterized by the presence of two confined domains, which are different in their cellular properties, biochemical functions and molecular identity. The generation of asymmetric domains in neurons should logically require specialized membrane trafficking to both promote neurite outgrowth and differential distribution of components. Members of the Rab family of small GTPases are key regulators of membrane trafficking involved in transport, tethering and docking of vesicles through their effectors. RabGTPases activity is coupled to the activity of guanine nucleotide exchange factors or GEFs, and GTPase-activating proteins known as GAPs. Since the overall spatiotemporal distribution of GEFs, GAPs and Rabs governs trafficking through the secretory and endocytic pathways, affecting exocytosis, endocytosis and endosome recycling, it is likely that RabGTPases could have a major role in neurite outgrowth, elongation and polarization. In this review we summarize the evidence linking the functions of several RabGTPases to axonal and dendritic development in primary neurons, as well as neurite formation in neuronal cell lines. We focused on the role of RabGTPases from the trans-Golgi network (TNG), early/late and recycling endosomes, as well as the function of some Rab effectors in neuritogenesis. Finally, we also discuss the participation of the ADP-ribosylation factor 6 (Arf6), a member of the ArfGTPase family, in neurite formation since it seems to have an important cross-talk with RabGTPases. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 02/2014; 129(2). DOI:10.1111/jnc.12676 · 4.28 Impact Factor
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    • "Animal DENN proteins have been shown to function as Rab guanine nucleotide exchange factors (GEFs), which activate Rabs by stimulating release of GDP and binding of GTP (Grosshans et al., 2006; Yoshimura et al., 2010). In particular, connecdenn 1, 2, and 3/DENND1A, B, and C are clathrin-coated vesicle (CCV)–associated GEFs for Rab35 (Allaire et al., 2010; Marat and McPherson, 2010), which function in CCV trafficking, endosomal recycling, actin regulation, and cytokinesis in animals (Kouranti et al., 2006; Patino-Lopez et al., 2008; Sato et al., 2008; Zhang et al., 2009). "
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    ABSTRACT: STOMATAL CYTOKINESIS DEFECTIVE1 (SCD1) encodes a putative Rab guanine nucleotide exchange factor that functions in membrane trafficking and is required for cytokinesis and cell expansion in Arabidopsis thaliana. Here, we show that the loss of SCD2 function disrupts cytokinesis and cell expansion and impairs fertility, phenotypes similar to those observed for scd1 mutants. Genetic and biochemical analyses showed that SCD1 function is dependent upon SCD2 and that together these proteins are required for plasma membrane internalization. Further specifying the role of these proteins in membrane trafficking, SCD1 and SCD2 proteins were found to be associated with isolated clathrin-coated vesicles and to colocalize with clathrin light chain at putative sites of endocytosis at the plasma membrane. Together, these data suggest that SCD1 and SCD2 function in clathrin-mediated membrane transport, including plasma membrane endocytosis, required for cytokinesis and cell expansion.
    The Plant Cell 10/2013; 25(10). DOI:10.1105/tpc.113.115162 · 9.34 Impact Factor
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    • "The multifaceted roles of Rabs, and the overlapping processes that they regulate, makes it difficult to correlate any specific Rab to a particular process. For example, diverse mechanisms such as phagocytosis, exocytosis and cell migration all require recycling of membranes, and consequently Rabs such as Rab35 and Rab8a have reported roles in all of these processes [14,17,26,89,90]. Clearly we need to develop a better understanding of the intricate roles of Rabs, their diverse and often cell-type specific effectors, and the dynamic membrane sorting events involved in these varied mechanisms. "
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    ABSTRACT: The regulation of Rab expression to modulate cellular function has recently been proposed. Dendritic cells are a prototypic example of cells that drastically alter their function in response to environmental cues by reducing endocytosis, secreting cytokines, changing surface protein repertoires and altering morphology and migration. This is not a binary event, but is subject to fluctuations through the activation process, termed maturation. Consequently, DCs transiently increase endocytosis and production of major histocompatibility complex class II molecules, and secrete inflammatory cytokines in infected tissues before migrating to secondary lymph nodes and releasing T cell polarizing factors. All these cellular processes rely on intracellular membrane transport, which is regulated by Rab family GTPases and their diverse effectors. Here we examine how the Rabs likely to be involved in these functions are regulated throughout DC maturation. We find that Rab expression is altered upon lipopolysaccharide-induced activation, and discuss how this correlates to the reported functions of these cells during maturation.
    PLoS ONE 09/2013; 8(9):e73538. DOI:10.1371/journal.pone.0073538 · 3.23 Impact Factor
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