Aggresomes and Russell bodies

Abstract

All cells are equipped with a proteolytic apparatus that eliminates damaged, misfolded and incorrectly assembled proteins. The principal engine of cytoplasmic proteolysis, the 26S proteasome, requires that substrates be unfolded to gain access to the active site; consequently, it is relatively ineffective at degrading aggregated proteins. Cellular indigestion occurs when the production of aggregation-prone proteins exceeds the cell's (or organelle's) capacity to eliminate them. Cellular pathways that resolve this indigestion exist, but appear to have limited capacities. Russell bodies and aggresomes are manifestations of cellular indigestion in the endoplasmic reticulum and cytoplasmic compartments, respectively, and are often associated with disease.

Desmin-related cardiomyopathy in transgenic mice: A cardiac amyloidosis

“…The aggregates, which are transported retrogradely on the microtubules and accumulate in the perinuclear region, have been termed aggresomes (21,22). Aggresomes have been detected in many diseases, including aging-related neurodegeneration and systemic amyloidosis (22,23). To explore the hypothesis that the electron-dense bodies present in the DRMs are indistinguishable from and can be defined as aggresomes, we developed a cell culture-based assay system in which CryAB aggregate formation could be studied in detail.…”

“…However, they rapidly accrete around the microtubule organizing center adjacent to the nucleus (20). This process is active, and it involves binding of the protoaggresomes to dynein motors and their subsequent retrograde transport along the microtubule network (23). Although composition can vary, the aggresomes are common cytopathological features in neurodegenerative, protein aggregation-related pathologies, and they usually contain components of the proteasome, molecular chaperones, ubiquitin conjugates, and intermediate filament proteins (23).…”

Quality control in the endoplasmic reticulum protein factory

“…At least two bottlenecks are encountered by ERAD substrates: dislocation across the membrane and actual degradation by the proteasome. Inefficient proteolysis often results in the formation of deposits of ubiquitylated proteins in the pericentriolar region, called aggresomes 30 . Studies with the prion protein suggest that mislocalization to the cytosol is sufficient to cause conversion into the PrP sc form 31,32 .…”

“…In plant cells, dilated ER cisternae are used for protein storage. In mammalian cells, they are generally associated with the accumulation of mutated or transport-incompetent proteins produced in excess with respect to ERAD capacity (for example, Russell bodies, RB 30 ). Additional ER subdomains were identified recently, including a peroxisome precursor compartment (P) and the cortical ER (CER) in yeast 40,41 .…”

“…For instance, different complexes of ER folding factors in the ER may fulfil sequential (and often opposite) tasks during protein maturation in the ER, and membrane sub-domains might exist. teins 30 . It is not clear whether these aberrant structures are toxic per se or whether they represent a defence mechanism that segregates dangerous proteins into specialized ER subcompartments (Fig.…”