title: Nonmuscle myosin IIB links cytoskeleton to IRE1α signaling during ER stress.
abstract: Here we identify and characterize a cytoskeletal myosin protein required for IRE1α oligomerization, activation, and signaling. Proteomic screening identified nonmuscle myosin heavy chain IIB (NMHCIIB), a subunit of nonmuscle myosin IIB (NMIIB), as an ER stress-dependent interacting protein specific to IRE1α. Loss of NMIIB compromises XBP1s and UPR target gene expression with no effect on the PERK pathway. Mechanistically, NMIIB is required for IRE1α aggregation and foci formation under ER stress. The NMIIB-mediated effect on IRE1α signaling is in part dependent on the phosphorylation of myosin regulatory light chain and the actomyosin contractility of NMIIB. Biologically, the function of NMIIB in ER stress response is conserved as both mammalian cells and C. elegans lacking NMIIB exhibit hypersensitivity to ER stress. Thus, optimal IRE1α activation and signaling require concerted coordination between the ER and cytoskeleton.
authors.affiliation: Graduate Program in Genetics, Genomics, and Development, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: He
authors.forename: Alexander
authors.initials: A
authors.lastname: Beatty
authors.forename: Xuemei
authors.initials: X
authors.lastname: Han
authors.forename: Yewei
authors.initials: Y
authors.lastname: Ji
authors.forename: Xuefei
authors.initials: X
authors.lastname: Ma
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kemphues
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D004722:Endoribonucleases / Q000378:metabolism*; D051379:Mice; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004722:Endoribonucleases; D018995:Myosin Heavy Chains; D024501:Nonmuscle Myosin Type IIB; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase; C000605544:Xbp1 protein, mouse; C510185:Ern1 protein, mouse; C103815:nonmuscle myosin type IIB heavy chain