Characterization of the human GARP (Golgi associated retrograde protein) complex

Liewen, Heike; Meinhold‐Heerlein, Ivo; Oliveira, Vasco; Schwarzenbacher, Robert; Luo, Guopei; Wadle, Andreas; Jung, Martin; Pfreundschuh, Michael; Stenner, Frank

doi:10.1016/j.yexcr.2005.01.022

Cited by 110 publications

(125 citation statements)

References 28 publications

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“…Mammalian GARP complex has recently been identified (61). Immunostaining of human GARP proteins shows an endosomal distribution and is most concentrated at the perinuclear region.…”

Section: Multisubunit Tethering Complexesmentioning

confidence: 99%

Role of tethering factors in secretory membrane traffic

Sztul¹,

Lupashin²

2006

American Journal of Physiology-Cell Physiology

169

143

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Sztul, Elizabeth, and Vladimir Lupashin. Role of tethering factors in secretory membrane traffic. Am J Physiol Cell Physiol 290: C11-C26, 2006; doi:10.1152/ ajpcell.00293.2005.-Coiled-coil and multisubunit tethers have emerged as key regulators of membrane traffic and organellar architecture. The restricted subcellular localization of tethers and their ability to interact with Rabs and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) suggests that tethers participate in determining the specificity of membrane fusion. An accepted model of tether function considers them molecular "bridges" that link opposing membranes before SNARE pairing. This model has been extended by findings in various experimental systems, suggesting that tethers may have other functions. Recent reports implicate tethers in the assembly of SNARE complexes, cargo selection and transit, cytoskeletal events, and localized attachment of regulatory proteins. A concept of tethers as scaffolding machines that recruit protein components involved in varied cellular responses is emerging. In this model, tethers function as integration switches that simultaneously transmit information to coordinate distinct processes required for membrane traffic. membrane tethering INTENSE INVESTIGATION over the past few decades has produced a general framework of the organelles and the factors regulating cargo transport from the endoplasmic reticulum (ER) to the plasma membrane (PM). Initial electron microscopic studies and more recent usage of light and live imaging have identified secretory compartments that handle cargo as it travels to the cell surface. All secretory and transmembrane proteins enter the pathway at the ER and are then sequentially transported through the ER-Golgi intermediate compartment (ERGIC), the Golgi complex, and the trans-Golgi network (TGN) before reaching the PM. Transport between the compartments occurs through small vesicles or larger tubulovesicular and tubular structures.In all cases, cargo is selected from the donor compartment by being sorted into a vesicle or a larger intermediate that then detaches from the donor compartment. The separation of cargo from resident proteins is mediated by the spatially restricted recruitment of coats. All coats studied to date are recruited to membranes by the active GTP-bound forms of the Sar1/ARF family of small GTPases (reviewed in Ref. 14). The recruitment of the coat is coupled to the sorting of the cargo into a transport intermediate. The sorting of cargo for export from the ER is mediated by the coat protein complex II (COPII) and the Sar1 GTPase. The sorting of cargo for exit from the TGN is mediated by clathrin and the ARF and Arl GTPases. An additional COPI coat recruited by ARF mediates protein sorting at the ERGIC and the Golgi. Available evidence indicates that COPI mediates the recycling of cellular components and does not directly participate in cargo sorting.After budding from the donor compartment, the transport intermediates traverse a certain distan...

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“…Mammalian GARP complex has recently been identified (61). Immunostaining of human GARP proteins shows an endosomal distribution and is most concentrated at the perinuclear region.…”

Section: Multisubunit Tethering Complexesmentioning

confidence: 99%

Role of tethering factors in secretory membrane traffic

Sztul¹,

Lupashin²

2006

American Journal of Physiology-Cell Physiology

169

143

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“…22 hVps53 (Human Vps53) or HCCS1 was demonstrated to have analogous characteristics to the yeast homologs, 23 and is expressed at a relatively low level in normal cells. Figure 1b indicated that although some cancer cells express deficient or significantly lower levels of HCCS1 due to its mutation and deletion on chromosome, other cancer cells can also express normal levels of HCCS1.…”

Section: Antitumor Effect Of Adenovirus Expressing Hccs1mentioning

confidence: 99%

Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on human colorectal cancer and hepatoma cells both in vitro and in vivo

Gan

Cai

et al. 2008

Cancer Gene Ther

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We had characterized earlier the novel tumor suppressor gene hepatocellular carcinoma suppressor 1 (HCCS1), and demonstrated that expression of exogenous HCCS1 gene in human hepatocarcinoma cells could remarkably suppress their abilities to develop tumors in nude mice and to form colonies in soft agar. In this study, we provide further experimental evidence to confirm the role of HCCS1 as a tumor suppressor gene and investigate its potential in therapeutic applications by using adenovirus vectors. We show that HCCS1 overexpression, mediated by replication-deficient adenovirus, significantly suppressed the growth of human colorectal cancer cells, as well as hepatocellular carcinoma cells in vitro and in vivo. To further improve its antitumor efficacy, we inserted the HCCS1 gene into an oncolytic adenovirus. This HCCS1-armed oncolytic adenovirus exhibited a dramatic inhibitory effect on cancer cells in vitro and in vivo, and led to a complete regression of 50% of established tumor xenografts in nude mice. Taken together, our data suggest that HCCS1 is a promising therapeutic gene for the treatment of human cancers.

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“…The wobbler mouse, carrying a mutation in the vacuolarvesicular protein sorting S4 (Vps54) gene (18) coding for a protein involved in the retrograde transport of late endosomes from the periphery to the Golgi apparatus (19), shows early-onset selective motor neuron death in the cervical spinal cord (reviewed in [20]). Glial activation (21)(22)(23) and upregulation of tumor necrosis factor (TNF)-α (24) have been reported in the cervical spinal cord of presymptomatic or early symptomatic mice.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Toll-Like Receptor 4 Antagonism in Spinal Cord Cultures and in a Mouse Model of Motor Neuron Degeneration

Paola

Mariani

Bigini

et al. 2012

Mol Med

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Sustained inflammatory reactions are common pathological events associated with neuron loss in neurodegenerative diseases. Reported evidence suggests that Toll-like receptor 4 (TLR4) is a key player of neuroinflammation in several neurodegenerative diseases. However, the mechanisms by which TLR4 mediates neurotoxic signals remain poorly understood. We investigated the role of TLR4 in in vitro and in vivo settings of motor neuron degeneration. Using primary cultures from mouse spinal cords, we characterized both the proinflammatory and neurotoxic effects of TLR4 activation with lipopolysaccharide (activation of microglial cells, release of proinflammatory cytokines and motor neuron death) and the protective effects of a cyanobacteriaderived TLR4 antagonist (VB3323). With the use of TLR4-deficient cells, a critical role of the microglial component with functionally active TLR4 emerged in this setting. The in vivo experiments were carried out in a mouse model of spontaneous motor neuron degeneration, the wobbler mouse, where we preliminarily confirmed a protective effect of TLR4 antagonism. Compared with vehicle-and riluzole-treated mice, those chronically treated with VB3323 showed a decrease in microglial activation and morphological alterations of spinal cord neurons and a better performance in the paw abnormality and grip-strength tests. Taken together, our data add new understanding of the role of TLR4 in mediating neurotoxicity in the spinal cord and suggest that TLR4 antagonists could be considered in future studies as candidate protective agents for motor neurons in degenerative diseases.

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Characterization of the human GARP (Golgi associated retrograde protein) complex

Cited by 110 publications

References 28 publications

Role of tethering factors in secretory membrane traffic

Role of tethering factors in secretory membrane traffic

Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on human colorectal cancer and hepatoma cells both in vitro and in vivo

Neuroprotective Effects of Toll-Like Receptor 4 Antagonism in Spinal Cord Cultures and in a Mouse Model of Motor Neuron Degeneration

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