The Interaction of Two Tethering Factors, p115 and COG complex, is Required for Golgi Integrity

Sohda, Miwa; Misumi, Yoshio; Yoshimura, Sho; Nakamura, Nobuhiro; Fusano, Takami; Ogata, Shigenori; Sakisaka, Shotaro; Ikehara, Yukio

doi:10.1111/j.1600-0854.2006.00530.x

Cited by 75 publications

(99 citation statements)

References 40 publications

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“…Depletion of Cog3 in HeLa cells resulted in the accumulation of COG complexdependent (CCD) vesicles carrying Golgi v-SNARE proteins but no anterograde cargo molecules (Zolov and Lupashin, 2005). Consistent with a role in Golgi trafficking, COG subunits interact with intra-Golgi SNAREs, the COPI coat, small GTPases and other tethering proteins (Laufman et al, 2011;Sohda et al, 2007;Sohda et al, 2010;Suvorova et al, 2002).…”

Section: Introductionmentioning

confidence: 86%

Mutations inCog7affect Golgi structure, meiotic cytokinesis and sperm development duringDrosophilaspermatogenesis

Belloni

Sechi

Riparbelli

et al. 2012

Journal of Cell Science

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SummaryThe conserved oligomeric Golgi (COG) complex plays essential roles in Golgi function, vesicle trafficking and glycosylation. Deletions in the human COG7 gene are associated with a rare multisystemic congenital disorder of glycosylation that causes mortality within the first year of life. In this paper, we characterise the Drosophila orthologue of COG7 (Cog7). Loss-of-function Cog7 mutants are viable but male sterile. The Cog7 gene product is enriched in the Golgi stacks and in Golgi-derived structures throughout spermatogenesis. Mutations in the Cog7 gene disrupt Golgi architecture and reduce the number of Golgi stacks in primary spermatocytes. During spermiogenesis, loss of the Cog7 protein impairs the assembly of the Golgi-derived acroblast in spermatids and affects axoneme architecture. Similar to the Cog5 homologue, four way stop (Fws), Cog7 enables furrow ingression during cytokinesis. We show that the recruitment of the small GTPase Rab11 and the phosphatidylinositol transfer protein Giotto (Gio) to the cleavage site requires a functioning wild-type Cog7 gene. In addition, Gio coimmunoprecipitates with Cog7 and with Rab11 in the testes. Our results altogether implicate Cog7 as an upstream component in a gio-Rab11 pathway controlling membrane addition during cytokinesis.

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Section: Introductionmentioning

confidence: 86%

Mutations inCog7affect Golgi structure, meiotic cytokinesis and sperm development duringDrosophilaspermatogenesis

Belloni

Sechi

Riparbelli

et al. 2012

Journal of Cell Science

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“…Its knockdown results in fragmentation of the Golgi apparatus (20). Different regions of the p115 N terminus have been implicated in binding to SNAREs, Rab1, and more recently COG2 (18,29,30) although how these interactions are integrated to mediate Golgi assembly is still not well understood. Additionally, the C terminus of p115 has been shown to bind GM130 and giantin via an ϳ30 residue highly acidic domain and these interactions were proposed to mediate post-mitotic Golgi assembly (31,32).…”

Section: Nuclear Translocation Of the P115 Ctf Is Required Formentioning

confidence: 99%

Nuclear Import Is Required for the Pro-apoptotic Function of the Golgi Protein p115

Mukherjee

Shields

2009

Journal of Biological Chemistry

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During apoptosis the Golgi apparatus undergoes irreversible fragmentation. In part, this results from caspase-mediated cleavage of several high molecular weight coiled-coil proteins, termed golgins. These include GM130, golgin 160, and the Golgi vesicle tethering protein p115, whose caspase cleavage generates a C-terminal fragment (CTF) of 205 residues. Here we demonstrate that early during apoptosis, following the rapid cleavage of p115, endogenous CTF translocated to the cell nucleus and its nuclear import was required to enhance the apoptotic response. Expression of a series of deletion constructs identified a putative ␣-helical region of 26 amino acids, whose expression alone was sufficient to induce apoptosis; deletion of these 26 residues from the CTF diminished its proapoptotic activity. This region contains several potential SUMOylation sites and co-expression of SUMO together with the SUMO ligase, UBC9, resulted in SUMOylation of the p115 CTF. Significantly, when cells were treated with drugs that induce apoptosis, SUMOylation enhanced the efficiency of p115 cleavage and the kinetics of apoptosis. A construct in which a nuclear export signal was fused to the N terminus of p115 CTF accumulated in the cytoplasm and surprisingly, its expression did not induce apoptosis. In contrast, treatment of cells expressing this chimera with the antibiotic leptomycin induced its translocation into the nucleus and resulted in the concomitant induction of apoptosis. These results demonstrate that nuclear import of the p115 CTF is required for it to stimulate the apoptotic response and suggest that its mode of action is confined to the nucleus.In mammalian cells the Golgi apparatus is a highly polarized organelle comprising a series of stacked cisternae, which form a lace-like network in the perinuclear region of the cell. It receives de novo synthesized secretory and membrane proteins, as well as lipids from the endoplasmic reticulum (ER) 2 ; these cargo molecules are then modified, sorted, and transported to lysosomes, endosomes, secretory granules, and the plasma membrane. Although it is well established that the Golgi apparatus undergoes reversible disassembly during mitosis (1, 2), indeed this appears to be a prerequisite for mitosis (3), studies from several laboratories including our own, have also established a link between the Golgi apparatus and apoptosis (programmed cell death). During apoptosis, the Golgi apparatus undergoes extensive and irreversible fragmentation (4), the ER vesiculates (5) and secretion is inhibited (6). Golgi disassembly during apoptosis results, in part, from caspase-mediated cleavage of several golgins (7). Proteolysis of golgin 160 by caspase-2, as well as GRASP65, GM130, p115, syntaxin5, and giantin by caspases-3 and -7 contributes significantly to Golgi fragmentation (6, 8 -13). Consistent with this idea, overexpression of caspase-resistant forms of golgin 160, GRASP65, or p115 has been shown to delay the kinetics of Golgi fragmentation during apoptosis (8 -10). In addition, immunore...

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“…The formation of this tethering complex further facilitates subsequent membrane docking through p115 interactions with various SNAREs such as the v-and t-SNAREs GOS28 and syntaxin-5 (4). In addition, p115 also binds to the GTPase Rab1(5), COG (conserved oligomeric Golgi) complex (6) and ␤-COP (7), supporting its role as a tethering factor in membrane trafficking. The knockdown of p115 results in Golgi fragmentation (8), showing that its tethering properties are required for the proper maintenance of Golgi structure and morphology.…”

mentioning

confidence: 99%

Tethering Function of the Caspase Cleavage Fragment of Golgi Protein p115 Promotes Apoptosis via a p53-dependent Pathway

How

Shields

2011

Journal of Biological Chemistry

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The Golgi apparatus undergoes extensive fragmentation during apoptosis due in part to caspase-mediated cleavage of its structural proteins. Significantly, the Golgi-vesicle-tethering protein p115 is cleaved at Asp 757 early during apoptosis and the nuclear translocation of its 205 amino acid C-terminal fragment (CTF) precedes observable Golgi fragmentation. Nuclear localization of the p115 CTF induces apoptosis. The regulation of CTF nuclear translocation and the mechanism of its apoptotic activity however, remain unknown. Here, we demonstrate that nuclear translocation of the CTF is regulated by SUMOylation. CTF-induced apoptosis is transcription dependent and mediated by the tumor suppressor, p53. Expression of the CTF led to the phosphorylation and stabilization of p53 and results in the expression of PUMA, a pro-apoptotic target of p53. CTF-induced stabilization of p53 is sensitive to the MEK/ERK inhibitor U0126. Co-immunoprecipitation studies indicate that the p115 CTF can bind to both p53 and ERK1. The CTF is also able to form dimers and its dimerization is dependent on residues 859 -884, previously determined to be required for apoptosis. Indeed, CTF expression promotes p53-ERK interaction, which is diminished upon deletion of residues 859 -884. Together, our results indicate a conserved tethering function of the Golgi protein p115 CTF which promotes p53-ERK interaction for the amplification of the apoptotic signal.

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The Interaction of Two Tethering Factors, p115 and COG complex, is Required for Golgi Integrity

Cited by 75 publications

References 40 publications

Mutations inCog7affect Golgi structure, meiotic cytokinesis and sperm development duringDrosophilaspermatogenesis

Mutations inCog7affect Golgi structure, meiotic cytokinesis and sperm development duringDrosophilaspermatogenesis

Nuclear Import Is Required for the Pro-apoptotic Function of the Golgi Protein p115

Tethering Function of the Caspase Cleavage Fragment of Golgi Protein p115 Promotes Apoptosis via a p53-dependent Pathway

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