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

2010 ◽  
Vol 286 (10) ◽  
pp. 8565-8576 ◽  
Author(s):  
Poh Choo How ◽  
Dennis Shields
Keyword(s):  
Caspase Cleavage ◽  
Cleavage Fragment ◽  
Golgi Protein ◽  
Dependent Pathway

scholarly journals Manganese-induced Trafficking and Turnover of the cis-Golgi Glycoprotein GPP130

2010 ◽  
Vol 21 (7) ◽  
pp. 1282-1292 ◽  
Author(s):  
Somshuvra Mukhopadhyay ◽  
Collin Bachert ◽  
Donald R. Smith ◽  
Adam D. Linstedt
Keyword(s):  
Mammalian Cells ◽  
Essential Element ◽  
Multivesicular Bodies ◽  
Low Concentrations ◽  
Early Endosomes ◽  
Rapid Changes ◽  
Golgi Protein ◽  
Elevated Exposure ◽  
Dependent Pathway ◽  
Mn Concentrations

Manganese is an essential element that is also neurotoxic at elevated exposure. However, mechanisms regulating Mn homeostasis in mammalian cells are largely unknown. Because increases in cytosolic Mn induce rapid changes in the localization of proteins involved in regulating intracellular Mn concentrations in yeast, we were intrigued to discover that low concentrations of extracellular Mn induced rapid redistribution of the mammalian cis-Golgi glycoprotein Golgi phosphoprotein of 130 kDa (GPP130) to multivesicular bodies. GPP130 was subsequently degraded in lysosomes. The Mn-induced trafficking of GPP130 occurred from the Golgi via a Rab-7–dependent pathway and did not require its transit through the plasma membrane or early endosomes. Although the cytoplasmic domain of GPP130 was dispensable for its ability to respond to Mn, its lumenal stem domain was required and it had to be targeted to the cis-Golgi for the Mn response to occur. Remarkably, the stem domain was sufficient to confer Mn sensitivity to another cis-Golgi protein. Our results identify the stem domain of GPP130 as a novel Mn sensor in the Golgi lumen of mammalian cells.

Inhibition of Tau Polymerization by Its Carboxy-Terminal Caspase Cleavage Fragment†

Biochemistry ◽  
2003 ◽  
Vol 42 (27) ◽  
pp. 8325-8331 ◽  
Author(s):  
R. W. Berry ◽  
A. Abraha ◽  
S. Lagalwar ◽  
N. LaPointe ◽  
T. C. Gamblin ◽  
...  
Keyword(s):  
Caspase Cleavage ◽  
Cleavage Fragment ◽  
Carboxy Terminal ◽  
Tau Polymerization

scholarly journals COPI selectively drives maturation of the early Golgi

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Effrosyni Papanikou ◽  
Kasey J Day ◽  
Jotham Austin ◽  
Benjamin S Glick
Keyword(s):  
Membrane Proteins ◽  
Fluorescence Microscopy ◽  
Secretory Pathway ◽  
Coated Vesicles ◽  
Peripheral Membrane Proteins ◽  
Video Fluorescence Microscopy ◽  
Golgi Protein ◽  
Dependent Pathway

COPI coated vesicles carry material between Golgi compartments, but the role of COPI in the secretory pathway has been ambiguous. Previous studies of thermosensitive yeast COPI mutants yielded the surprising conclusion that COPI was dispensable both for the secretion of certain proteins and for Golgi cisternal maturation. To revisit these issues, we optimized the anchor-away method, which allows peripheral membrane proteins such as COPI to be sequestered rapidly by adding rapamycin. Video fluorescence microscopy revealed that COPI inactivation causes an early Golgi protein to remain in place while late Golgi proteins undergo cycles of arrival and departure. These dynamics generate partially functional hybrid Golgi structures that contain both early and late Golgi proteins, explaining how secretion can persist when COPI has been inactivated. Our findings suggest that cisternal maturation involves a COPI-dependent pathway that recycles early Golgi proteins, followed by multiple COPI-independent pathways that recycle late Golgi proteins.

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

2002 ◽  
Vol 159 (4) ◽  
pp. 637-648 ◽  
Author(s):  
Raymond Chiu ◽  
Leonid Novikov ◽  
Shaeri Mukherjee ◽  
Dennis Shields
Keyword(s):  
Golgi Apparatus ◽  
Mammalian Cells ◽  
Resistant Mutant ◽  
Apoptotic Response ◽  
Caspase Cleavage ◽  
Vesicle Tethering ◽  
Cleavage Fragment ◽  
Resistant Form ◽  
Golgi Fragmentation

In mammalian cells, the Golgi apparatus undergoes extensive fragmentation during apoptosis. p115 is a key vesicle tethering protein required for maintaining the structural organization of the Golgi apparatus. Here, we demonstrate that p115 was cleaved during apoptosis by caspases 3 and 8. Compared with control cells expressing native p115, those expressing a cleavage-resistant form of p115 delayed Golgi fragmentation during apoptosis. Expression of cDNAs encoding full-length or an NH2-terminal caspase cleavage fragment of p115 had no effect on Golgi morphology. In contrast, expression of the COOH-terminal caspase cleavage product of p115 itself caused Golgi fragmentation. Furthermore, this fragment translocated to the nucleus and its expression was sufficient to induce apoptosis. Most significantly, in vivo expression of the COOH-terminal fragment in the presence of caspase inhibitors, or upon coexpression with a cleavage-resistant mutant of p115, showed that p115 degradation plays a key role in amplifying the apoptotic response independently of Golgi fragmentation.

The Mechanism of Platelet Aggregation Induced by HLA-Related Antibodies

1996 ◽  
Vol 76 (05) ◽  
pp. 774-779 ◽  
Author(s):  
John T Brandt ◽  
Carmen J Julius ◽  
Jeanne M Osborne ◽  
Clark L Anderson
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Complement Activation ◽  
Thromboembolic Disease ◽  
Clinical Samples ◽  
Hla Antigen ◽  
Aggregation Response ◽  
Immune Mediated ◽  
Dependent Pathway

SummaryImmune-mediated platelet activation is emerging as an important pathogenic mechanism of thrombosis. In vitro studies have suggested two distinct pathways for immune-mediated platelet activation; one involving clustering of platelet FcyRIIa, the other involving platelet-associated complement activation. HLA-related antibodies have been shown to cause platelet aggregation, but the mechanism has not been clarified. We evaluated the mechanism of platelet aggregation induced by HLA-related antibodies from nine patients. Antibody to platelet FcyRIIa failed to block platelet aggregation with 8/9 samples, indicating that engagement of platelet FcyRIIa is not necessary for the platelet aggregation induced by HLA-related antibodies. In contrast, platelet aggregation was blocked by antibodies to human C8 (5/7) or C9 (7/7). F(ab’)2 fragments of patient IgG failed to induce platelet activation although they bound to HLA antigen on platelets. Intact patient IgG failed to aggregate washed platelets unless aged serum was added. The activating IgG could be adsorbed by incubation with lymphocytes and eluted from the lymphocytes. These results indicate that complement activation is involved in the aggregation response to HLA-related antibodies. This is the first demonstration of complement-mediated platelet aggregation by clinical samples. Five of the patients developed thrombocytopenia in relationship to blood transfusion and two patients developed acute thromboembolic disease, suggesting that these antibodies and the complement-dependent pathway of platelet aggregation may be of clinical significance.

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