Increased expression and retention of the secretory chaperone proSAAS following cell stress

Cell Stress Chaperones. 2020 Nov;25(6):929-941. doi: 10.1007/s12192-020-01128-7. Epub 2020 Jul 20.


The secretory pathway of neurons and endocrine cells contains a variety of mechanisms designed to combat cellular stress. These include not only the unfolded protein response pathways but also diverse chaperone proteins that collectively work to ensure proteostatic control of secreted and membrane-bound molecules. One of the least studied of these chaperones is the neural- and endocrine-specific molecule known as proSAAS. This small chaperone protein acts as a potent anti-aggregant both in vitro and in cellulo and also represents a cerebrospinal fluid biomarker in Alzheimer's disease. In the present study, we have examined the idea that proSAAS, like other secretory chaperones, might represent a stress-responsive protein. We find that exposure of neural and endocrine cells to the cell stressors tunicamycin and thapsigargin increases cellular proSAAS mRNA and protein in Neuro2A cells. Paradoxically, proSAAS secretion is inhibited by these same drugs. Exposure of Neuro2A cells to low concentrations of the hypoxic stress inducer cobalt chloride, or to sodium arsenite, an oxidative stressor, also increases cellular proSAAS content and reduces its secretion. We conclude that the cellular levels of the small secretory chaperone proSAAS are positively modulated by cell stress.

Keywords: Cell stress; Cell viability; PCSK1N; Secretory chaperones; proSAAS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arsenites / pharmacology
  • Cell Hypoxia / drug effects
  • Cell Line
  • Cobalt / pharmacology
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects
  • Heat-Shock Proteins / metabolism
  • Mice
  • Molecular Chaperones / metabolism*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Sodium Compounds / pharmacology
  • Stress, Physiological* / drug effects
  • Thapsigargin / pharmacology
  • Tunicamycin / pharmacology
  • Up-Regulation / drug effects


  • Arsenites
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Neuropeptides
  • Pcsk1n protein, mouse
  • Protective Agents
  • RNA, Messenger
  • Sodium Compounds
  • Tunicamycin
  • Cobalt
  • sodium arsenite
  • Thapsigargin
  • cobaltous chloride