RRC ID 59427
Author Zha J, Ying M, Alexander-Floyd J, Gidalevitz T.
Title HSP-4/BiP expression in secretory cells is regulated by a developmental program and not by the unfolded protein response.
Journal PLoS Biol
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.
Volume 17(3)
Pages e3000196
Published 2019-3-1
DOI 10.1371/journal.pbio.3000196
PMID 30908491
PMC PMC6448932
MeSH Animals B-Lymphocytes / metabolism Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Cell Differentiation / genetics Cell Differentiation / physiology Endoplasmic Reticulum / genetics Endoplasmic Reticulum / metabolism Heat-Shock Proteins / genetics Heat-Shock Proteins / metabolism* Repressor Proteins / metabolism Signal Transduction / genetics Signal Transduction / physiology Unfolded Protein Response / genetics Unfolded Protein Response / physiology*
IF 8.386
Times Cited 1
C.elegans tm4063