VRK2A is an A-type lamin–dependent nuclear envelope kinase that phosphorylates BAF

نویسندگان

  • Birendra KC
  • Danielle G. May
  • Benjamin V. Benson
  • Dae In Kim
  • Winnie G. Shivega
  • Manaal H. Ali
  • Randolph S. Faustino
  • Alexandre R. Campos
  • Kyle J. Roux
چکیده

The nuclear envelope (NE) is critical for numerous fundamental cellular functions, and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis of lamin A, Sun2 and a minimal INM-targeting motif. These studies identify vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM. The transmembrane VRK2A isoform is retained at the NE by association with A-type lamins. Furthermore, VRK2A physically interacts with A-type, but not B-type, lamins. Finally, we show that VRK2 phosphorylates barrier to autointegration factor (BAF), a small and highly dynamic chromatin-binding protein, which has roles including NE reassembly, cell cycle, and chromatin organization in cells, and subtly alters its nuclear mobility. Together these findings support the value of using BioID to identify unrecognized constituents of distinct subcellular compartments refractory to biochemical isolation and reveal VRK2A as a transmembrane kinase in the NE that regulates BAF.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Presumed pseudokinase VRK3 functions as a BAF kinase.

Vaccinia-related kinase 3 (VRK3) is known as a pseudokinase that is catalytically inactive due to changes in motifs that are essential for kinase activity. Although VRK3 has been regarded as a genuine pseudokinase from structural and biochemical studies, recent reports suggest that VRK3 acts as an active kinase as well as a signaling scaffold in cells. Here, we demonstrate that VRK3 phosphoryla...

متن کامل

Role of emerin and protein kinase C in herpes simplex nuclear egress

The nuclear lamina consists of a mesh-like network of lamin proteins anchored to the inner nuclear membrane by interactions with integral membrane proteins such as emerin. Emerin is a member of the LEM domain family, members of which interact with BAF. LEM domain protein-BAF interactions create a bridge between the INM and chromatin, which aids in reassembly of the nuclear envelope after mitosi...

متن کامل

A complex containing p34cdc2 and cyclin B phosphorylates the nuclear lamin and disassembles nuclei of clam oocytes in vitro

Cell-free extracts prepared from activated clam oocytes contain factors which induce phosphorylation of the single 67-kD lamin (L67), disassemble clam oocyte nuclei, and cause chromosome condensation in vitro (Dessev, G., R. Palazzo, L. Rebhun, and R. Goldman. 1989. Dev. Biol. 131:469-504). To identify these factors, we have fractionated the oocyte extracts. The nuclear lamina disassembly (NLD)...

متن کامل

NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus

Accurate chromosome segregation in meiosis requires dynamic changes in chromatin organization. In Drosophila melanogaster, upon completion of recombination, meiotic chromosomes form a single, compact cluster called the karyosome in an enlarged oocyte nucleus. This clustering is also found in humans; however, the mechanisms underlying karyosome formation are not understood. In this study, we rep...

متن کامل

Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF.

Loss of emerin, a lamin-binding nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy. We analyzed 13 site-directed mutations, and four disease-causing mutations that do not disrupt emerin stability or localization. We show that emerin binds directly to barrier-to-autointegration factor (BAF), a DNA-bridging protein, and that this binding to BAF requires conserved residues in the L...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 28  شماره 

صفحات  -

تاریخ انتشار 2017