Transcellular chaperone signaling: an organismal strategy for integrated cell stress responses

Abstract

The ability of each cell within a metazoan to adapt to and survive environmental and physiological stress requires cellular stressresponse mechanisms, such as the heat shock response (HSR). Recent advances reveal that cellular proteostasis and stress responses in metazoans are regulated by multiple layers of intercellular communication. This ensures that an imbalance of proteostasis that occurs within any single tissue 'at risk' is protected by a compensatory activation of a stress response in adjacent tissues that confers a community protective response. While each cell expresses the machinery for heat shock (HS) gene expression, the HSR is regulated cell non-autonomously in multicellular organisms, by neuronal signaling to the somatic tissues, and by transcellular chaperone signaling between somatic tissues and from somatic tissues to neurons. These cell non-autonomous processes ensure that the organismal HSR is orchestrated across multiple tissues and that transmission of stress signals between tissues can also override the neuronal control to reset cell-and tissue-specific proteostasis. Here, we discuss emerging concepts and insights into the complex cell non-autonomous mechanisms that control stress responses in metazoans and highlight the importance of intercellular communication for proteostasis maintenance in multicellular organisms.

The Chaperone Activity of the Developmental Small Heat Shock Protein Sip1 Is Regulated by pH-Dependent Conformational Changes

“…The observation that the depletion of sip1 already leads to a stress response in the worm (as visible by the overexpression of the hsp16 genes), might explain why a further stress situation, like heat stress or aging, has severe effects on embryonic and adult worms. In the worm, it has been shown that there is a crosstalk between different tissues and organs concerning the stress status (van Oosten-Hawle and Morimoto, 2014). In agreement to the present study, this seems to apply for the reproductive tissue of the adult and the embryo.…”

Dynamic O-Linked N-Acetylglucosamine Modification of Proteins Affects Stress Responses and Survival of Mesothelial Cells Exposed to Peritoneal Dialysis Fluids

“…The activation of HSF-1, the key transcription factor of Hsp72, is a multistep process involving multiple regulators that might be independently regulated by factors prevalent in PDF. 48,49 O-GlcNAc-mediated regulation of HSF-1 is also supported by the recent work by Kazemi et al, 23 which reported a link between Hsp72, HSF-1, glycogen synthase kinase 3b, and O-GlcNAcylation. Recently, we have shown that the addition of glutamine to PDF protects mesothelial cells in in vitro and in vivo models of PD by enhancing CSRs after PDF exposure.…”

Microbial pathogenesis and host defense in the nematode C. elegans

“…C. elegans has no known dedicated, migratory immune cells like macrophages to aid in defense against infection of the intestine or epidermis, and does not appear to have canonical cytokine and chemokine signaling pathways used to recruit those cells. However, C. elegans does use system-wide signaling to respond to stress and infection by upregulating defense pathways in epithelial cells, which is a topic that has been covered in other reviews [9,12,18-21]. …”