The discovery and consequences of the central role of the nervous system in the control of protein homeostasis

Abstract

Organisms function despite wide fluctuations in their environment through the maintenance of homeostasis. At the cellular level, the maintenance of proteins as functional entities at target expression levels is called protein homeostasis (or proteostasis). Cells implement proteostasis through universal and conserved quality control mechanisms that surveil and monitor protein conformation. Recent studies that exploit the powerful ability to genetically manipulate specific neurons in C. elegans have shown that cells within this metazoan lose their autonomy over this fundamental survival mechanism. These studies have uncovered novel roles for the nervous system in controlling how and when cells activate their protein quality control mechanisms. Here we discuss the conceptual underpinnings, experimental evidence and the possible consequences of such a control mechanism. PRELUDE: Whether the detailed examination of parts of the nervous system and their selective perturbation is sufficient to reconstruct how the brain generates behavior, mental disease, music and religion remains an open question. Yet, Sydney Brenner’s development of C. elegans as an experimental organism and his faith in the bold reductionist approach that ‘the understanding of wild-type behavior comes best after the discovery and analysis of mutations that alter it’, has led to discoveries of unexpected roles for neurons in the biology of organisms.

Keywords:

• Homeostasis
• proteostasis
• non-autonomous
• neuronal
• C. elegans

Acknowledgements

We thank the members of V.P. laboratory and Dr. Tali Gidalevitz (Drexel University) for useful comments. We apologize to all our colleagues whose work we may have omitted to cite.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by NIH R01 AG 050653 (V.P.).