Regulation of small heat-shock proteins by hetero-oligomer formation

Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results

“…Overall, the current picture is that the dynamic oligomeric architecture allows, by regulating the accessibility of the client-binding surfaces, sHSPs to flexibly utilize different binding modes while protecting them from inappropriate interactions and aggregation [17,166,167,171,179,180]. The equilibrium between monomers, dimers, and oligomers, and hence the chaperone activity, can be regulated by phosphorylation [138,161,167,169,172,176,[181][182][183][184] and stress-related environmental factors such as temperature [185,186], pH [179,187], metal ions [188], and the redox state [171].…”

“…The equilibrium between monomers, dimers, and oligomers, and hence the chaperone activity, can be regulated by phosphorylation [138,161,167,169,172,176,[181][182][183][184] and stress-related environmental factors such as temperature [185,186], pH [179,187], metal ions [188], and the redox state [171]. The system can be fine-tuned by hetero-oligomerization, which is thought to offer an optimal combination of stability and chaperone activity [17,180]. In addition, BAG3 binding has been recently shown to dissociate HSPB1 oligomers, allowing it to modulate sHSP function [16].…”

“…HSPB1 is mostly present as polydisperse oligomers of 400-600 kDa [172,190], whose dramatic dissolution to smaller species is associated with the phosphorylation of the NTD [172,176,[297][298][299], increased temperature [299], and oxidative conditions [300,301]. It interacts with CRYAB and HSPB6, and it forms hetero-oligomers in tissues coexpressing these sHSPs [17,19,180,302,303]. In muscle, HSPB1 shows a similar expression pattern and localization to CRYAB, albeit its absolute levels are lower [197,198,203].…”

Homeostatic Roles of the Proteostasis Network in Dendrites

“…The differing function between two such closely related chaperones is exemplary of the diversity of the small Hsp family. The small Hsp family is, ironically, one of the largest families of chaperones, with ten members in humans -HSPB1-10 -that all have diverse protein clients and are expressed in an array of tissues throughout the body, though most are expressed in the brain as well (Carra et al, 2012;Mymrikov et al, 2020). Traditionally thought of as chaperones that act as holdases to prevent protein aggregation in cell stress conditions, it has been discovered that several small Hsps contribute to proper dendritic arborization in homeostatic conditions (Narberhaus, 2002;Bakthisaran et al, 2015).…”

“…Small heat shock proteins are known to group together in hetero-and homo-oligomers, although the function of these oligomers is not yet known (Nefedova et al, 2015;Mymrikov et al, 2020). The interaction of chaperones may be the key to regulation of neuronal processes.…”