Evidence for regulation of ER/Golgi SNARE complex formation by hsc70 chaperones

Joglekar, Ashwini P.; Hay, Jesse

doi:10.1016/j.ejcb.2004.12.028

Cited by 19 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNAJB2 belongs to the DNAJ/HSP40 co-chaperone family which is an ATP-dependent positive regulator of HSP70 and plays a central role in the cellular stress response. Hspa8 encodes a member of the HSP70 family which seems to provide antigrowth inhibitory role, as demonstrated by knockdown studies [73]. Hsp90b1 encodes 90 kDa heat shock protein which plays a role in protecting cells from undergoing apoptosis, and mediating immunogenicity in tumor [74,75].…”

Section: Discussionmentioning

confidence: 99%

Nano-sized titanium dioxide-induced splenic toxicity: A biological pathway explored using microarray technology

Sheng

Wang

Sang

et al. 2014

Journal of Hazardous Materials

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Nano-sized titanium dioxide-induced splenic toxicity: A biological pathway explored using microarray technology

Sheng

Wang

Sang

et al. 2014

Journal of Hazardous Materials

View full text Add to dashboard Cite

“…For example, Hsp27, Hsp90 and Hsp70 control the oligomeric state and thus the activity of many native proteins, such as clathrin cages [42][43], SNARES [44] and complexes involved in the signal transduction of steroids and of heat-shock [45,46]. Moreover, Hsp70, Bip, and possibly ClpC serve as motor components of the cellular machinery, translocating pre-proteins from the cytoplasm into the mitochondria, the endoplasmic reticulum and chloroplasts, respectively [47][48][49].…”

Section: Molecular Chaperones and Proteases Neutralize And Detoxify Pmentioning

confidence: 99%

Disaggregating Chaperones: An Unfolding Story

Sharma¹,

Christen²,

Goloubinoff

2009

CPPS

100

View full text Add to dashboard Cite

Stress, molecular crowding and mutations may jeopardize the native folding of proteins. Misfolded and aggregated proteins not only loose their biological activity, but may also disturb protein homeostasis, damage membranes and induce apoptosis. Here, we review the role of molecular chaperones as a network of cellular defenses against the formation of cytotoxic protein aggregates. Chaperones favour the native folding of proteins either as "holdases", sequestering hydrophobic regions in misfolding polypeptides, and/or as "unfoldases", forcibly unfolding and disentangling misfolded polypeptides from aggregates. Whereas in bacteria, plants and fungi Hsp70/40 acts in concert with the Hsp100 (ClpB) unfoldase, Hsp70/40 is the only known chaperone in the cytoplasm of mammalian cells that can forcibly unfold and neutralize cytotoxic protein conformers. Owing to its particular spatial configuration, the bulky 70 kDa Hsp70 molecule, when distally bound through a very tight molecular clamp onto a 50-fold smaller hydrophobic peptide loop extruding from an aggregate, can locally exert on the misfolded segment an unfolding force of entropic origin, thus destroying the misfolded structures that stabilize aggregates. ADP/ATP exchange triggers Hsp70 dissociation from the ensuing enlarged unfolded peptide loop, which is then allowed to spontaneously refold into a closer-to-native conformation devoid of affinity for the chaperone. Driven by ATP, the cooperative action of Hsp70 and its co-chaperone Hsp40 may thus gradually convert toxic misfolded protein substrates with high affinity for the chaperone, into non-toxic, natively refolded, low-affinity products. Stress- and mutation-induced protein damages in the cell, causing degenerative diseases and aging, may thus be effectively counteracted by a powerful network of molecular chaperones and of chaperone-related proteases.

show abstract

“…Molecular chaperones also activate or inhibit various signaling pathways [14–16]. For example, Hsc70 regulates SNARE complexes [17, 18]. After exocytosis, when the cis -SNARE complex is stuck on the target membrane, the AAA+ ATPase N -ethylmaleimide sensitive factor disassembles it and after disassembly, Hsc70 together with cysteine-string protein-alpha and small guanine-rich tetratricopeptide protein, are then required for the refolding of the SNARE SNAP-25, converting it into an active form [19].…”

Section: The Role Of Chaperones In Protein Misfolding Diseasesmentioning

confidence: 99%

“…Other J-domain proteins can bind to alternatively folded substrates, such as sigma 32 [150], and SNARES that are substrates that do not tend to aggregate under physiological conditions. Likewise, auxilin is a J-protein that can bind only to the alternatively folded clathrin cages and Pam16/18 of the mitochondrial import pore do not directly bind to any substrate protein per se but only indirectly by way of the nearby pore [18, 20, 151, 152]. Rather, J-domain proteins principally act as chaperone targeting devices.…”

Section: Chaperones With Targetase Activitymentioning

confidence: 99%

Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins

Mattoo

Goloubinoff

2014

Cell. Mol. Life Sci.

109

View full text Add to dashboard Cite

By virtue of their general ability to bind (hold) translocating or unfolding polypeptides otherwise doomed to aggregate, molecular chaperones are commonly dubbed “holdases”. Yet, chaperones also carry physiological functions that do not necessitate prevention of aggregation, such as altering the native states of proteins, as in the disassembly of SNARE complexes and clathrin coats. To carry such physiological functions, major members of the Hsp70, Hsp110, Hsp100, and Hsp60/CCT chaperone families act as catalytic unfolding enzymes or unfoldases that drive iterative cycles of protein binding, unfolding/pulling, and release. One unfoldase chaperone may thus successively convert many misfolded or alternatively folded polypeptide substrates into transiently unfolded intermediates, which, once released, can spontaneously refold into low-affinity native products. Whereas during stress, a large excess of non-catalytic chaperones in holding mode may optimally prevent protein aggregation, after the stress, catalytic disaggregases and unfoldases may act as nanomachines that use the energy of ATP hydrolysis to repair proteins with compromised conformations. Thus, holding and catalytic unfolding chaperones can act as primary cellular defenses against the formation of early misfolded and aggregated proteotoxic conformers in order to avert or retard the onset of degenerative protein conformational diseases.

show abstract

Evidence for regulation of ER/Golgi SNARE complex formation by hsc70 chaperones

Cited by 19 publications

References 31 publications

Nano-sized titanium dioxide-induced splenic toxicity: A biological pathway explored using microarray technology

Nano-sized titanium dioxide-induced splenic toxicity: A biological pathway explored using microarray technology

Disaggregating Chaperones: An Unfolding Story

Molecular chaperones are nanomachines that catalytically unfold misfolded and alternatively folded proteins

Contact Info

Product

Resources

About