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Journal article
HSP-4/BiP expression in secretory cells is regulated by a developmental program and not by the unfolded protein response
PLoS biology, v 17(3), pp e3000196-e3000196
01 Mar 2019
PMID: 30908491
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Differentiation of secretory cells leads to sharp increases in protein synthesis, challenging endoplasmic reticulum (ER) proteostasis. Anticipatory activation of the unfolded protein response (UPR) prepares cells for the onset of secretory function by expanding the ER size and folding capacity. How cells ensure that the repertoire of induced chaperones matches their postdifferentiation folding needs is not well understood. We find that during differentiation of stem-like seam cells, a typical UPR target, the Caenorhabditis elegans immunoglobulin heavy chain-binding protein (BiP) homologue Heat-Shock Protein 4 (HSP-4), is selectively induced in alae-secreting daughter cells but is repressed in hypodermal daughter cells. Surprisingly, this lineage-dependent induction bypasses the requirement for UPR signaling. Instead, its induction in alae-secreting cells is controlled by a specific developmental program, while its repression in the hypodermal-fated cells requires a transcriptional regulator B-Lymphocyte-Induced Maturation Protein 1 (BLMP-1/BLIMP1), involved in differentiation of mammalian secretory cells. The HSP-4 induction is anticipatory and is required for the integrity of secreted alae. Thus, differentiation programs can directly control a broad-specificity chaperone that is normally stress dependent to ensure the integrity of secreted proteins.
Author summary During differentiation, cells that specialize in secretion of proteins, such as antibody-secreting B cells, prepare for the onset of secretory function by expanding the size of the major secretory organelle, the endoplasmic reticulum (ER), and by increasing the expression of molecular chaperones and folding enzymes. This pre-emptive expansion of the ER depends on activation of the ER stress response pathways and is required for the secretory phenotype. In addition, cells may also need to up-regulate a selected subset of chaperones because different secreted proteins may require different chaperones for their folding and secretion. Except in specialized cases, how this selective up-regulation is achieved, and whether it depends on the ER stress pathways, is not well understood. Using Caenorhabditis elegans, we find that a chaperone BiP/HSP-4, which is usually induced in most cells by stress, is selectively induced during differentiation of stem cells into the alae-secreting cells while being repressed in their sister lineage, the hypodermal cells. We find that induction of this chaperone is independent of the known ER stress pathways, while its repression requires a known regulator of development in mammals, BLIMP1/BLMP-1. The pre-emptive induction of BiP/HSP-4 is important for the integrity of secreted alae and cuticle, suggesting that a general molecular chaperone that is a canonical target of ER stress pathways can be selectively regulated by development to ensure the quality of secreted proteome and functionality of the cells postdifferentiation.
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Details
- Title
- HSP-4/BiP expression in secretory cells is regulated by a developmental program and not by the unfolded protein response
- Creators
- Ji Zha - Drexel UniversityMingjie Ying - Drexel UniversityJasmine Alexander-Floyd - Drexel UniversityTali Gidalevitz - Drexel University
- Publication Details
- PLoS biology, v 17(3), pp e3000196-e3000196
- Publisher
- Public Library Science
- Number of pages
- 23
- Grant note
- P40 OD010440 / National Institutes of Health (NIH) Office of Research Infrastructure Programs P40OD010440 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000462993700034
- Scopus ID
- 2-s2.0-85064285585
- Other Identifier
- 991019167917404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology