DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior

J Cell Biol. 2015 Mar 2;208(5):629-48. doi: 10.1083/jcb.201407068. Epub 2015 Feb 23.


The small guanosine triphosphatase Rab13 functions in exocytic vesicle trafficking in epithelial cells. Alterations in Rab13 activity have been observed in human cancers, yet the mechanism of Rab13 activation and its role in cancer progression remain unclear. In this paper, we identify the DENN domain protein DENND2B as the guanine nucleotide exchange factor for Rab13 and develop a novel Förster resonance energy transfer-based Rab biosensor to reveal activation of Rab13 by DENND2B at the leading edge of migrating cells. DENND2B interacts with the Rab13 effector MICAL-L2 at the cell periphery, and this interaction is required for the dynamic remodeling of the cell's leading edge. Disruption of Rab13-mediated trafficking dramatically limits the invasive behavior of epithelial cells in vitro and the growth and migration of highly invasive cancer cells in vivo. Thus, blocking Rab13 activation by DENND2B may provide a novel target to limit the spread of epithelial cancers.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement*
  • Humans
  • Mice
  • Mice, Nude
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology
  • Protein Transport / genetics
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*


  • MICALL2 protein, human
  • Microfilament Proteins
  • RAB31 protein, human
  • Tumor Suppressor Proteins
  • rab GTP-Binding Proteins

Associated data

  • GENBANK/BC028064
  • GENBANK/BC036655
  • GENBANK/BC036864
  • GENBANK/BC098407