Update on Brefeldin A Brefeldin A: Deciphering an Enigmatic Inhibitor of Secretion

نویسندگان

  • Andreas Nebenführ
  • Christophe Ritzenthaler
  • David G. Robinson
چکیده

The fungal macrocyclic lactone brefeldin A (BFA) has proved to be of great value as an inhibitor of protein trafficking in the endomembrane system of mammalian cells (Sciaky et al., 1997). BFA has also often been used as an inhibitor of secretion and vacuolar protein transport in plant cells, but just exactly how BFA achieves these effects has been a matter of debate for some time (e.g. Satiat-Jeunemaitre et al., 1996; Staehelin and Driouich, 1997). The apparently broad spectrum of BFA responses, combined with a lack of understanding of the primary target of BFA, has made it difficult to develop a coherent explanation of BFA effects, which in turn has led to a series of misconceptions that riddle the plant literature. In the last few years, there has been a tremendous increase in our understanding of the molecular targets and primary effects of BFA in mammalian and yeast systems (see below). On the plant side, several papers have recently been published that, by applying new tools and technologies, have shed fresh light onto the BFA problem (Baluska et al., 2002; Brandizzi et al., 2002; Emans et al., 2002; Ritzenthaler et al., 2002; Saint-Jore et al., 2002). In this Update, we wish to evaluate these new findings and explore whether we are any closer to solving the dilemma of “what BFA really does.”

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Brefeldin A: deciphering an enigmatic inhibitor of secretion.

The fungal macrocyclic lactone brefeldin A (BFA) has proved to be of great value as an inhibitor of protein trafficking in the endomembrane system of mammalian cells (Sciaky et al., 1997). BFA has also often been used as an inhibitor of secretion and vacuolar protein transport in plant cells, but just exactly how BFA achieves these effects has been a matter of debate for some time (e.g. Satiat-...

متن کامل

Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes.

We examined the effect of brefeldin A, an antiviral antibiotic, on protein synthesis, intracellular processing, and secretion in primary culture of rat hepatocytes. The secretion was strongly blocked by the drug at 1 microgram/ml and higher concentrations, while the protein synthesis was maintained fairly well. Pulse-chase experiments with [35S]methionine demonstrated that brefeldin A completel...

متن کامل

Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL.

Previous studies showed that chronic lymphocytic leukemia (CLL) cells exhibit certain mitochondrial abnormalities including mtDNA mutations, increased superoxide generation, and aberrant mitochondrial biogenesis, which are associated with impaired apoptosis and reduced sensitivity to fludarabine. Here we report that CLL cells and multiple myeloma cells are highly sensitive to brefeldin A, an in...

متن کامل

Prevention of brefeldin A-induced resistance to teniposide by the proteasome inhibitor MG-132: involvement of NF-kappaB activation in drug resistance.

Brefeldin A, an agent that disrupts protein transport from the endoplasmic reticulum to the Golgi, induces the expression of GRP78 and the activation of nuclear factor (NF)-kappaB in cells. Treatment of cells with brefeldin A causes the development of resistance to topoisomerase II-directed agents, such as etoposide and doxorubicin. In this study, we show that treatment of EMT6 mouse mammary tu...

متن کامل

Brefeldin A defines distinct pathways for atrial natriuretic factor secretion in neonatal rat atrial and ventricular myocytes.

The intracellular pathways for basal atrial natriuretic factor (ANF) secretion from the heart and their correlation with ANF processing to the active form were characterized in cultured neonatal rat atrial and ventricular myocytes. Brefeldin A, a fungal antimetabolite that blocks transport of newly synthesized proteins from the endoplasmic reticulum, was used to inhibit nascent protein traffick...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2002