title: ELYS regulates the localization of LBR by modulating its phosphorylation state.
abstract: Lamin B receptor (LBR), an inner nuclear membrane (INM) protein, contributes to the functional integrity of the nucleus by tethering heterochromatin to the nuclear envelope. We have previously reported that the depletion of embryonic large molecule derived from yolk sac (ELYS; also known as AHCTF1), a component of the nuclear pore complex, from cells perturbs the localization of LBR to the INM, but little is known about the underlying molecular mechanism. In this study, we found that the depletion of ELYS promoted LBR phosphorylation at the residues known to be phosphorylated by cyclin-dependent kinase (CDK) and serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2, respectively). These phosphorylation events were most likely to be counter-balanced by protein phosphatase 1 (PP1), and the depletion of PP1 from cells consistently caused the mislocalization of LBR. These observations point to a new mechanism regulating the localization of LBR, which is governed by an ELYS-mediated phosphorylation network. This phosphorylation-dependent coordination between INM proteins and the nuclear pore complex might be important for the integrity of the nucleus.
authors: Cellular Dynamics Laboratory, Riken, Saitama 351-0198, Japan.
authors: Yasuhiro
authors: Y
authors: Mimura
authors: Cellular Dynamics Laboratory, Riken, Saitama 351-0198, Japan.
authors: Masatoshi
authors: M
authors: Takagi
authors: Cellular Dynamics Laboratory, Riken, Saitama 351-0198, Japan.
authors: Michaela
authors: M
authors: Clever
authors: Cellular Dynamics Laboratory, Riken, Saitama 351-0198, Japan nimamoto@riken.jp.
authors: Naoko
authors: 0000-0002-2886-3022
authors: N
authors: Imamoto
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D034921:Lamin Type B / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D000072417:Protein Domains; D020033:Protein Isoforms / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000097682:Lamin B Receptor
chemical_list: D016203:CDC2 Protein Kinase; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D034921:Lamin Type B; D009687:Nuclear Proteins; D020033:Protein Isoforms; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000097682:Lamin B Receptor; C517876:AHCTF1 protein, human
keywords: Inner nuclear membrane protein; Nuclear envelope; Nuclear pore complex; Nucleoporin; Phosphorylation