Coupling of ER exit to microtubules through direct interaction of COPII with dynactin

Watson, Peter; Forster, Rebecca; Palmer, Krysten J.; Pepperkok, Rainer; Stephens, David

doi:10.1038/ncb1206

Cited by 159 publications

(168 citation statements)

References 33 publications

(48 reference statements)

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“…The budded vesicles are then transported from ERES to the ER-Golgi intermediate compartment (ER-GIC) in a COPII-dependent step, and at ERGIC they are fused to form vesicular-tubular transport carriers (VTC) and finally transported to the cis-Golgi in a second COPII-and dynein-dependent step [43,44]. Disruption of interaction between COPII complex and dynactin, a dynein adaptor linking dynein to cargoes, inhibits cargo export from the ER, but does not affect the motility of VTCs [44]. This study suggests that ER export may be dynein dependent.…”

Section: Discussionmentioning

confidence: 99%

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Kong

Peng

et al. 2013

Cell Res

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Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtubules within eukaryotic cells. However, in mammals, few mutants are available for studying the effects of defects in dynein-controlled processes in the context of the whole organism. Here, we deleted mouse Dlic1 gene encoding DLIC1, a subunit of the dynein complex. Dlic1 −/− mice are viable, but display severe photoreceptor degeneration. Ablation of Dlic1 results in ectopic accumulation of outer segment (OS) proteins, and impairs OS growth and ciliogenesis of photoreceptors by interfering with Rab11-vesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body. Our studies show that Dlic1 deficiency partially blocks vesicle export from endoplasmic reticulum (ER), but seems not to affect vesicle transport from the ER to Golgi. Further mechanistic study reveals that lack of Dlic1 destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors, probably due to the impaired transport function of dynein. Our results demonstrate that Dlic1 plays important roles in ciliogenesis and protein transport to the OS, and is required for photoreceptor development and survival. The Dlic1 −/− mice also provide a new mouse model to study human retinal degeneration.

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Section: Discussionmentioning

confidence: 99%

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Kong

Peng

et al. 2013

Cell Res

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“…Although there is some controversy over whether the ERGIC itself or membrane carriers derived from it traverse between the ER to the Golgi complex (compare Ben-Tayaka et al, 2004, with Murshid andPresley, 2004), it is clear that this transport occurs along microtubules. In fact, the actual process of ER exit is tightly coupled to the presence of microtubules via an interaction between the COPII-coat protein Sec23 and dynein/dynactin motor protein complexes (Watson et al, 2004). In distinct contrast, ER-to-Golgi transport in plants occurs across a short interface and is independent of microtubules (Nebenfü hr et al, 2000;Saint-Jore et al, 2002).…”

Section: Golgi Regeneration Is Not Cytoskeleton Dependentmentioning

confidence: 99%

Golgi Regeneration after Brefeldin A Treatment in BY-2 Cells Entails Stack Enlargement and Cisternal Growth followed by Division

et al. 2007

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Brefeldin A (BFA) treatment stops secretion and leads to the resorption of much of the Golgi apparatus into the endoplasmic reticulum. This effect is reversible upon washing out the drug, providing a situation for studying Golgi biogenesis. In this investigation Golgi regeneration in synchronized tobacco BY-2 cells was followed by electron microscopy and by the immunofluorescence detection of ARF1, which localizes to the rims of Golgi cisternae and serves as an indicator of COPI vesiculation. Beginning as clusters of vesicles that are COPI positive, mini-Golgi stacks first become recognizable 60 min after BFA washout. They continue to increase in terms of numbers and length of cisternae for a further 90 min before overshooting the size of control Golgi stacks. As a result, increasing numbers of dividing Golgi stacks were observed 120 min after BFA washout. BFA-regeneration experiments performed on cells treated with BFA (10 mg mL 21 ) for only short periods (30-45 min) showed that the formation of ER-Golgi hybrid structures, once initiated by BFA treatment, is an irreversible process, the further incorporation of Golgi membranes into the ER continuing during a subsequent drug washout. Application of the protein kinase A inhibitor H-89, which effectively blocks the reassembly of the Golgi apparatus in mammalian cells, also prevented stack regeneration in BY-2 cells, but only at very high, almost toxic concentrations (.200 mM). Our data suggest that under normal conditions mitosis-related Golgi stack duplication may likely occur via cisternal growth followed by fission.

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“…Interaction of SEC23 with the outer coat stimulates the GAP activity and accelerates the GTP hydrolysis of SAR1. After SAR1 release, SEC23 interacts with the TRAPPI complex subunits BET3 and dynactin, suggesting a function in vesicle tethering, fusion, and transportation along microtubules (14,15). Finally, phosphorylation of SEC23 is thought to facilitate the fusion of COPII vesicles with the target membrane (16).…”

mentioning

confidence: 99%

SEC23B is required for the maintenance of murine professional secretory tissues

Tao

Zhu

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

105

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In eukaryotic cells, newly synthesized secretory proteins require COPII (coat protein complex II) to exit the endoplasmic reticulum (ER). COPII contains five core components: SAR1, SEC23, SEC24, SEC13, and SEC31. SEC23 is a GTPase-activating protein that activates the SAR1 GTPase and also plays a role in cargo recognition. Missense mutations in the human COPII paralogues SEC23A and SEC23B result in craniolenticulosutural dysplasia and congenital dyserythropoietic anemia type II, respectively. We now report that mice completely deficient for SEC23B are born with no apparent anemia phenotype, but die shortly after birth, with degeneration of professional secretory tissues. In SEC23B-deficient embryonic pancreas, defects occur in exocrine and endocrine tissues shortly after differentiation. Pancreatic acini are completely devoid of zymogen granules, and the ER is severely distended. Similar ultrastructural alterations are also observed in salivary glands, but not in liver. Accumulation of proteins in the ER lumen activates the proapoptotic pathway of the unfolded protein response, suggesting a central role for apoptosis in the degeneration of these tissues in SEC23B-deficient embryos. Although maintenance of the secretory pathway should be required by all cells, our findings reveal a surprising tissue-specific dependence on SEC23B for the ER exit of highly abundant cargo, with high levels of SEC23B expression observed in professional secretory tissues. The disparate phenotypes in mouse and human could result from residual SEC23B function associated with the hypomorphic mutations observed in humans, or alternatively, might be explained by a species-specific shift in function between the closely related SEC23 paralogues. mammalian embryo abnormalities | vesicular transport protein | genetics | secretory granules | pancreatitis I n eukaryotic cells, secreted proteins and proteins that are targeted to the plasma membrane and internal organelles are synthesized in the endoplasmic reticulum (ER) and sorted through the secretory pathway. This process has been extensively studied, particularly in budding yeast (1). Proteins destined to traffic from the ER to the Golgi are packaged into COPII (coat protein complex II)-coated vesicles (2-4). COPII is composed of at least five proteins, a small GTPase SAR1 and two cytosolic protein complexes, SEC23-SEC24 and SEC13-SEC31 (5). The GTP-bound form of SAR1 binds to the ER membrane and recruits the SEC23-SEC24 heterodimer to form the "prebudding complex," which in turn recruits the outer coat composed of SEC13-SEC31 heterotetramers to complete the COPII coat structure (6).The COPII complex captures cargo into vesicles and mediates vesicle budding from the ER. Cargo recognition appears to be mediated primarily by the SEC24 subunit, which recognizes divergent export signals located in the cytosolic domain of cargo proteins (7,8). SEC23 and SAR1 also play a role in the recognition of at least a subset of cargos (9, 10). SEC23 is a GTPaseactivating protein (GAP) that activates the SAR1...

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Coupling of ER exit to microtubules through direct interaction of COPII with dynactin

Cited by 159 publications

References 33 publications

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Golgi Regeneration after Brefeldin A Treatment in BY-2 Cells Entails Stack Enlargement and Cisternal Growth followed by Division

SEC23B is required for the maintenance of murine professional secretory tissues

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