A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis

Chiu, Raymond; Novikov, Leonid; Mukherjee, Shaeri; Shields, Dennis

doi:10.1083/jcb.200208013

Cited by 146 publications

(165 citation statements)

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“…A number of secretory pathway proteins are substrates for caspase cleavage, including BAP-31 in the ER (Ng et al, 1997), and golgin-160 (Mancini et al, 2000), giantin (Lowe et al, 2004), GRASP65 (Lane et al, 2002), and p115 (Chiu et al, 2002) at the Golgi. Besides contributing to organelle disassembly, cleavage of some of these proteins seems to be important for initiation of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Caspase cleavage of the Golgi t-SNARE syntaxin-5 (Lowe et al, 2004) and Golgilocalized components of the dynein-dynactin motor complex (Lane et al, 2001) have been implicated in termination of membrane trafficking during apoptosis. Expression of caspase-resistant mutants of golgin-160, GRASP65, or p115 delays Golgi disassembly during apoptosis (Mancini et al, 2000;Chiu et al, 2002;Lane et al, 2002). Expression of a construct mimicking the C-terminal caspase-cleavage product of p115 causes Golgi fragmentation and induces apoptosis (Chiu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Expression of caspase-resistant mutants of golgin-160, GRASP65, or p115 delays Golgi disassembly during apoptosis (Mancini et al, 2000;Chiu et al, 2002;Lane et al, 2002). Expression of a construct mimicking the C-terminal caspase-cleavage product of p115 causes Golgi fragmentation and induces apoptosis (Chiu et al, 2002). These results indicate an important role for caspase cleavage of Golgi-resident proteins during apoptosis and suggest involvement of Golgi-resident proteins, This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E04 -11-0971) on April 13, 2005. not just in execution of apoptotic disassembly but also in initiation of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas elements of mitotic and apoptotic Golgi disassembly seem to have features in common (Sesso et al, 1999), apoptotic Golgi disassembly is irreversible and primarily depends on protein cleavage rather than phosphorylation. During apoptosis, caspases cleave proteins involved in Golgi structure and trafficking, including golgin-160 (Mancini et al, 2000), GM130 (Nozawa et al, 2002;Lowe et al, 2004), giantin (Lowe et al, 2004), GRASP65 (Lane et al, 2002), and p115 (Chiu et al, 2002).Cleavage of Golgi-resident proteins seems to be important for cessation of membrane trafficking, Golgi disassembly, and possibly initiation of apoptosis. Caspase cleavage of the Golgi t-SNARE syntaxin-5 (Lowe et al, 2004) and Golgilocalized components of the dynein-dynactin motor complex (Lane et al, 2001) have been implicated in termination of membrane trafficking during apoptosis.…”

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Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Maag

Mancini

Rosen

et al. 2005

MBoC

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Golgin-160 is a coiled-coil protein on the cytoplasmic face of the Golgi complex that is cleaved by caspases during apoptosis. We assessed the sensitivity of cell lines stably expressing wild-type or caspase-resistant golgin-160 to several proapoptotic stimuli. Cells expressing a caspase-resistant mutant of golgin-160 were strikingly resistant to apoptosis induced by ligation of death receptors and by drugs that induce endoplasmic reticulum (ER) stress, including brefeldin-A, dithiothreitol, and thapsigargin. However, both cell lines responded similarly to other proapoptotic stimuli, including staurosporine, anisomycin, and etoposide. The caspase-resistant golgin-160 dominantly prevented cleavage of endogenous golgin-160 after ligation of death receptors or induction of ER stress, which could be explained by a failure of initiator caspase activation. The block in apoptosis in cells expressing caspase-resistant golgin-160 could not be bypassed by expression of potential caspase cleavage fragments of golgin-160, or by drug-induced disassembly of the Golgi complex. Our results suggest that some apoptotic signals (including those initiated by death receptors and ER stress) are sensed and integrated at Golgi membranes and that golgin-160 plays an important role in transduction of these signals. INTRODUCTIONThe Golgi complex is central to the regulation of membrane trafficking in eukaryotic cells. It is the primary site for sorting and processing of proteins undergoing both exocytosis and endocytosis (reviewed in Farquhar and Palade, 1998). Under normal conditions, the mammalian Golgi complex is a collection of stacks of cisternal membranes near the microtubule organizing center. Proteins traversing the secretory pathway enter the Golgi at the cis face, are processed as they pass through the Golgi stacks, and are sorted at the trans face into vesicles bound for their intended destinations. The trans-Golgi is also important in sorting proteins being endocytosed or cycling between the plasma membrane and intracellular membrane compartments. This affords the Golgi extensive communication with the rest of the cell and its surroundings, placing it in a prime position to sense and integrate information about the state of the cell and its environment.The structure of the Golgi is highly dynamic, allowing reversible disassembly during mitosis. Key secretory pathway proteins are phosphorylated in a cell cycle-dependent manner to stop membrane trafficking and disassemble the Golgi (reviewed in Rabouille and Jokitalo, 2003). This rearrangement from a single perinuclear organelle to dispersed vesiculated compartments is thought to ensure partitioning of the Golgi complex into both daughter cells during cytokinesis. When Golgi disassembly is prevented by addition of antibodies to Golgi reassembly and stacking protein of 65 kDa (GRASP65), cells complete S phase, but they are unable to enter mitosis. This mitotic block can be bypassed by disassembling the Golgi with drugs (Sutterlin et al., 2002). Once mitosis is complete, the Golgi...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Maag

Mancini

Rosen

et al. 2005

MBoC

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Caspases, Substrates and Sequential Activation

Walsh¹,

Martin²

2009

Encyclopedia of Life Sciences

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Superfluous, aged or damaged cells are eliminated from tissues via a controlled cell death process, called apoptosis. Apoptosis is coordinated by a group of cysteine aspartic acid‐specific proteases (caspases) that become specifically activated within cells destined to die. Some of these proteases act as initiators, their role being to interface with signalling events and initiate the proteolytic cascade, whereas others act as executioner enzymes and carry out the internal dismantling of the cell that results in death. During the terminal phase of apoptosis the executioner caspases (caspases‐3 and ‐7) simultaneously cleave hundreds of protein substrates to terminate cell viability and produce the characteristic apoptotic phenotype. This large‐scale proteolysis also dismembers the cell into discrete fragments that are recognized and removed by scavenging phagocytes. Recent evidence also suggests that the actions of executioner caspases may disable molecules that are capable of initiating or exacerbating immune responses if released into the extracellular space. Key Concepts: Pro‐apoptotic stimuli lead to the activation of caspases. Caspase activation takes the form of a cascade of sequential activation events. Caspases mediate the structural changes characteristic of apoptotic cell death by processing key protein substrates. Caspase‐dependent demolition of the apoptotic cell facilitates its safe removal by surveying phagocytes.

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Apoptosis

Galmiche¹,

Zychlinsky²

2010

Topley &Amp; Wilson's Microbiology and Microbial Infections

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A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis

Cited by 146 publications

References 47 publications

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory Pathway Stress and Ligation of Death Receptors

Caspases, Substrates and Sequential Activation

Apoptosis

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