SUMOylation of human septins is critical for septin filament bundling and cytokinesis

J Cell Biol. 2017 Dec 4;216(12):4041-4052. doi: 10.1083/jcb.201703096. Epub 2017 Oct 19.

Abstract

Septins are cytoskeletal proteins that assemble into nonpolar filaments. They are critical in diverse cellular functions, acting as scaffolds for protein recruitment and as diffusion barriers for subcellular compartmentalization. Human septins are encoded by 13 different genes and are classified into four groups based on sequence homology (SEPT2, SEPT3, SEPT6, and SEPT7 groups). In yeast, septins were among the first proteins reported to be modified by SUMOylation, a ubiquitin-like posttranslational modification. However, whether human septins could be modified by small ubiquitin-like modifiers (SUMOs) and what roles this modification may have in septin function remains unknown. In this study, we first show that septins from all four human septin groups can be covalently modified by SUMOs. We show in particular that endogenous SEPT7 is constitutively SUMOylated during the cell cycle. We then map SUMOylation sites to the C-terminal domain of septins belonging to the SEPT6 and SEPT7 groups and to the N-terminal domain of septins from the SEPT3 group. We finally demonstrate that expression of non-SUMOylatable septin variants from the SEPT6 and SEPT7 groups leads to aberrant septin bundle formation and defects in cytokinesis after furrow ingression. Altogether, our results demonstrate a pivotal role for SUMOylation in septin filament bundling and cell division.

MeSH terms

  • Cell Compartmentation
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cytokinesis / genetics*
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Fluorescence Recovery After Photobleaching
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Microscopy, Video
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Phylogeny
  • Protein Processing, Post-Translational*
  • Septins / genetics*
  • Septins / metabolism
  • Sumoylation

Substances

  • Cell Cycle Proteins
  • Green Fluorescent Proteins
  • SEPTIN2 protein, human
  • SEPTIN6 protein, human
  • SEPTIN7 protein, human
  • Septins
  • septin 3