REEP3/4 ensure endoplasmic reticulum clearance from metaphase chromatin and proper nuclear envelope architecture

Dev Cell. 2013 Aug 12;26(3):315-23. doi: 10.1016/j.devcel.2013.06.016. Epub 2013 Aug 1.


Dynamic interactions between membrane-bound organelles and the microtubule cytoskeleton are crucial to establish, maintain, and remodel the internal organization of cells throughout the cell cycle. However, the molecular nature of these interactions remains poorly understood. We performed a biochemical screen for microtubule-membrane linkers and identified REEP4, a previously uncharacterized endoplasmic reticulum (ER) protein. Depletion of REEP4 and the closely related REEP3 from HeLa cells causes defects in cell division and a proliferation of intranuclear membranes derived from the nuclear envelope. This phenotype originates in mitosis, when ER membranes accumulate on metaphase chromosomes. Microtubule binding and mitotic ER clearance from chromosomes both depend on a short, positively charged amino acid sequence connecting the two hydrophobic domains of REEP4. Our results show that REEP3/4 function redundantly to clear the ER from metaphase chromatin, thereby ensuring correct progression through mitosis and proper nuclear envelope architecture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Nucleus / physiology
  • Chromatin / metabolism*
  • Chromosome Segregation / physiology
  • Endoplasmic Reticulum / physiology*
  • Green Fluorescent Proteins
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Interphase / physiology
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Metaphase / physiology*
  • Microtubules / metabolism
  • Mitosis / physiology
  • Molecular Sequence Data
  • Nuclear Envelope / physiology*


  • Chromatin
  • Membrane Transport Proteins
  • REEP3 protein, human
  • REEP4 protein, human
  • Green Fluorescent Proteins