A Differentiation Transcription Factor Establishes Muscle-Specific Proteostasis in Caenorhabditis elegans

• DOI: 10.1371/journal.pgen.1006531
• Publication Date: 2017-01-09T20:01:23Z
• Authors: Yael Bar-Lavan; Netta Shemesh; Shiran Dror; Rivka Ofir; Esti Yeger-Lotem; Anat Ben-Zvi
• Keywords: Proteostasis; Chaperone (clinical); Proteome

Safeguarding the proteome is central to health of cell. In multi-cellular organisms, composition proteome, and by extension, protein-folding requirements, varies between cells. agreement, chaperone network differs tissues. Here, we ask how expression regulated in a cell type-specific manner whether cellular differentiation affects expression. Our bioinformatics analyses show that myogenic transcription factor HLH-1 (MyoD) can bind promoters genes expressed or required for folding muscle proteins. To test this experimentally, employed potential genetically modulate Caenorhabditis elegans embryonic cells ectopically expressing all embryo monitoring We found HLH-1-dependent conversion specifically induced putative HLH-1-regulated chaperones differentiating Moreover, disrupting HLH-1-binding sites on ubiquitously daf-21(Hsp90) muscle-enriched hsp-12.2(sHsp) abolished their myogenic-dependent Disrupting function reduced compromised proteostasis during after embryogenesis. turn, modulating disrupted assembly proteins thus, myogenesis. muscle-specific over-expression DNAJB6 homolog DNJ-24, limb-girdle muscular dystrophy-associated chaperone, exposed synthetic motility defects. propose could establish dedicated maintenance proteome. Such cell-specific networks explain selective vulnerability many diseases protein misfolding exhibit even when misfolded expressed.