Table of Contents

Volume 1, Issue 4

  July - December 2011

  Pages 119 - 172

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LETTER FROM THE EDITOR

Open Access Article

A note from the Editor-in-Chief

Nava Segev
Page 119
http://dx.doi.org/10.4161/cl.1.4.18934
PDF




EDITORIAL

Open Access Article

Bringing host-cell takeover by pathogenic bacteria to center stage

Ron Dubreuil and Nava Segev
Pages 120 - 124
http://dx.doi.org/10.4161/cl.1.4.18984
Abstract | PDF

Intracellular pathogenic bacteria contrive processes in their host cell to create a niche for their own reproduction. One way that has emerged by which bacteria do that is delivery of secreted virulence factors, SVFs, to the cytoplasm of the host cells using the bacterial type IV secretion system, T4SS. These SVFs modulate the activity of their target host proteins, which in turn control key cellular processes. A major mechanism for the evolution of SVFs that modulate targets that do not exist in the bacterial kingdom is horizontal gene transfer. Recently, a number of bacterial SVFs were shown to act on two types of targets in host cells. First, a group of several SVFs modulate the activity and localization of one protein: Rab1 GTPase, a key regulator of intracellular trafficking. Second, ankyrin repeats-containing SVFs, referred to by microbiologists as Anks, interact with various binding proteins, which in turn regulate a myriad of cellular processes, including apoptosis. Modulation of trafficking and apoptosis are two examples of how invading bacteria takeover their host phagocyte, which instead of destroying the bacteria becomes a factory for its reproduction.




REVIEWS

Open Access Article

Take it and release it: the use of the Rab1 small GTPase at a bacterium's will

Yunhao Tan and Zhao-Qing Luo
Pages 125 - 127
http://dx.doi.org/10.4161/cl.1.4.17870
Abstract | PDF

Successful pathogens are equipped to exploit the signaling pathways of their host cell to establish a niche conducive for their survival and proliferation. One emerging example is the modulation of the small GTPase Rab1 by virulence factors of the intracellular pathogen Legionella pneumophila. Besides proteins that mimic host regulatory factors involved in controlling Rab1 activity, this bacterium temporally locks this small GTPase in its active form by AMPylation. Efficient release of Rab1 from the bacterial phagosome requires deAMPylation prior to being inactivated by the bacterial GAP protein LepB. Whether Rab activity is similarly regulated under native condition is unknown, but it is clear that virulence factors from pathogens can be invaluable tools in dissecting the intricacy of host cellular processes.



Note: An editorial about this paper can be found online at: www.landesbioscience.com/journals/cellularlogistics/article/18984

Open Access Article

ThANKs for the repeat: Intracellular pathogens exploit a common eukaryotic domain

Daniel Voth
Pages 128 - 132
http://dx.doi.org/10.4161/cl.1.4.18738
Abstract | PDF

Bacterial pathogens are renowned cell biologists that subvert detrimental host responses by manipulating eukaryotic protein function. A select group of pathogens use a specialized type IV secretion system (T4SS) as a conduit to deliver an arsenal of proteins into the host cytosol where they interact with host proteins. The translocated "effectors" have garnered increased attention because they uncover novel aspects of host-pathogen interactions at the subcellular level. This review presents a group of effectors termed Anks that possess eukaryotic-like ankyrin repeat domains that mediate protein-protein interactions and are critical for effector function. Interestingly, most known prokaryotic Anks are produced by bacteria that devote much of their time to replicating inside eukaryotic cells. Ank proteins represent a fascinating and versatile family of effectors exploited by bacterial pathogens and are proving useful as tools to study eukaryotic cell biology.

Note: An editorial about this paper can be found online at: www.landesbioscience.com/journals/cellularlogistics/article/18984

Open Access Article

Catch and release: Rab1 exploitation by Legionella pneumophila

Matthias P. Machner and Yang Chen
Pages 133 - 138
http://dx.doi.org/10.4161/cl.1.4.18933
Abstract | PDF

The intracellular pathogen Legionella pneumophila exploits host cell vesicular transport by manipulating the activity of the small GTPase Rab1. Bacterial proteins, so called effectors, that are delivered into the infected cell play a key role in this process. Here, we summarize recent developments in our quest to understand the molecular function of these effectors, and describe how L. pneumophila employs post-translational modification in a reversible manner to manipulate the activity of Rab1 on its vacuole.

Note: An editorial about this paper can be found online at: www.landesbioscience.com/journals/cellularlogistics/article/18984




RESEARCH PAPER

Open Access Article

ArfGAP1 promotes COPI vesicle formation by facilitating coatomer polymerization

Yoko Shiba, Ruibai Luo, Jenny E. Hinshaw, Tomasz Szul, Ryo Hayashi, Elizabeth Sztul, Kunio Nagashima, Ulrich Baxa and Paul A. Randazzo
Pages 139 - 154
http://dx.doi.org/10.4161/cl.1.4.18896
Abstract | PDF

The role of ArfGAP1 in COPI vesicle biogenesis has been controversial. In work using isolated Golgi membranes, ArfGAP1 was found to promote COPI vesicle formation. In contrast, in studies using large unilamellar vesicles (LUVs) as model membranes, ArfGAP1 functioned as an uncoating factor inhibiting COPI vesicle formation. We set out to discriminate between these models. First, we reexamined the effect of ArfGAP1 on LUVs. We found that ArfGAP1 increased the efficiency of coatomer-induced deformation of LUVs. Second, ArfGAP1 and peptides from cargo facilitated self-assembly of coatomer into spherical structures in the absence of membranes, reminiscent of clathrin self-assembly. Third, in vivo, ArfGAP1 overexpression induced the accumulation of vesicles and allowed normal trafficking of a COPI cargo. Taken together, these data support the model in which ArfGAP1 promotes COPI vesicle formation and membrane traffic and identify a function for ArfGAP1 in the assembly of coatomer into COPI.




ARTICLE ADDENDA

Open Access Article

Small GTPase Rab12 regulates transferrin receptor degradation: Implications for a novel membrane trafficking pathway from recycling endosomes to lysosomes

Takahide Matsui and Mitsunori Fukuda
Pages 155 - 158
http://dx.doi.org/10.4161/cl.1.4.18152
Abstract | PDF

Plasma membrane receptor proteins play a key role in signal transduction and nutrient uptake, thereby controlling quality of receptor proteins is one of the most important issues in cellular logistics. After endocytosis, receptor proteins are generally delivered to lysosomes for degradation or recycled back to the plasma membrane for recycling. Transferrin receptor (TfR) is a well-known representative of recycling receptor proteins, which are traveled between plasma membrane and recycling endosomes. Although the molecular mechanism of the TfR recycling pathway has been extensively investigated in the literature, almost nothing is known about its degradation mechanism. We have recently shown that small GTPase Rab12 and its upstream activator Dennd3 regulate the constitutive degradation of TfR without modulating a conventional endocytic degradation pathway or TfR recycling pathway. Our findings suggest that Rab12 regulates membrane trafficking of TfR from recycling endosomes to lysosomes. In this addendum, we discuss the physiological significance of TfR degradation and the fate of determination of TfR (recycling or degradation).

Open Access Article

Rab1b regulates COPI and COPII dynamics in mammalian cells

Iris A. García, Hernán E. Martinez and Cecilia Alvarez
Pages 159 - 163
http://dx.doi.org/10.4161/cl.1.4.18221
Abstract | PDF

Rabs GTPases are key regulatory factors that specifically associate to organelles that integrate membrane transport pathways. Rabs, through their interactions with diverse effector proteins, regulate the formation, movement, tethering and fusion of transport carriers (vesicles and/or tubules). The mammalian Rab1b GTPase is required for ER to Golgi transport and interacts with multiple effectors localized at the ER-Golgi interface. Here, we focus on interactions between Rab1b and effectors that play essential roles in COPII and COPI vesicle formation/function. Based on evidence to date, we propose a model of Rab1b action at the ER exit sites.

Open Access Article

Dual function of Sec16B: endoplasmic reticulum-derived protein secretion and peroxisome biogenesis in mammalian cells

Katsuko Tani, Mitsuo Tagaya, Shusuke Yonekawa and Takashi Baba
Pages 164 - 167
http://dx.doi.org/10.4161/cl.1.4.18341
Abstract | PDF

The origin of peroxisomes has long been disputed. However, recent evidence suggests that peroxisomes can be formed de novo from the endoplasmic reticulum (ER) in yeast and higher eukaryotes. Sec16A and Sec16B, mammalian orthologs of yeast Sec16, are scaffold proteins that organize ER exit sites by interacting with COPII components. We recently demonstrated that Sec16B, but not Sec16A, regulates the transport of peroxisomal biogenesis factors from the ER to peroxisomes in mammalian cells. The C-terminal region of Sec16B, which is not conserved in Sec16A, is required for this function. The data suggest that Sec16B in ER areas other than ER exit sites plays this role. Our findings provide an unexpected connection between at least part of the COPII machinery and the formation of pre-peroxisomal vesicles at the ER, and offer an explanation of how secretory and peroxisomal trafficking from the ER are distinguished.

Open Access Article

AP180 and CALM : dedicated endocytic adaptors for the retrieval of synaptobrevin 2 at synapses.

Seong Joo Koo, Dmytro Puchkov and Volker Haucke
Pages 168 - 172
http://dx.doi.org/10.4161/cl.1.4.18897
Abstract | PDF

Communication between neurons largely occurs at chemical synapses involving conversion of electric to chemical signals. Chemical neurotransmission involves the action potential-driven release of neurotransmitters from synaptic vesicles (SVs) at presynaptic nerve terminals. Fusion of SVs is driven by SNARE complex formation comprising synaptobrevin 2 on the SV membrane and syntaxin 1A and SNAP-25 on the plasma membrane. In order to maintain neurotransmission during repetitive stimulation and to prevent expansion of the presynaptic plasma membrane, exocytic SV fusion needs to be balanced by compensatory retrieval of SV components to regenerate functional vesicles. Our recent work has unraveled a mechanism by which the R-SNARE synaptobrevin 2, the most abundant SV protein and an essential player for exocytic fusion is recycled from the presynaptic membrane. The SNARE motif of synaptobrevin 2 is directly recognized by the ANTH domains of AP180 and CALM, monomeric endocytic adaptors for clathrin-mediated endocytosis. Given that key residues involved in synaptobrevin 2-ANTH domain complex formation are also essential for SNARE assembly, we propose that disassembly of SNARE complexes is a prerequisite for synaptobrevin 2 retrieval, thereby preventing endocytic mis-sorting of the plasma membrane Q-SNAREs syntaxin 1A and SNAP-25. It is tempting to speculate that perturbed synaptobrevin 2 recycling caused by reduction of CALM or AP180 levels may lead to disease as suggested by the genetic association of ANTH domain proteins with neurodegenerative disorders.