Focal defects in single-celled tubes mutant for Cerebral cavernous malformation 3, GCKIII, or NSF2

Dev Cell. 2013 Jun 10;25(5):507-19. doi: 10.1016/j.devcel.2013.05.002.


Tubes of differing cellular architecture connect into networks. In the Drosophila tracheal system, two tube types connect within single cells (terminal cells); however, the genes that mediate this interconnection are unknown. Here we characterize two genes that are essential for this process: lotus, required for maintaining a connection between the tubes, and wheezy, required to prevent local tube dilation. We find that lotus encodes N-ethylmaleimide sensitive factor 2 (NSF2), whereas wheezy encodes Germinal center kinase III (GCKIII). GCKIIIs are effectors of Cerebral cavernous malformation 3 (CCM3), a protein mutated in vascular disease. Depletion of Ccm3 by RNA interference phenocopies wheezy; thus, CCM3 and GCKIII, which prevent capillary dilation in humans, prevent tube dilation in Drosophila trachea. Ectopic junctional and apical proteins are present in wheezy terminal cells, and we show that tube dilation is suppressed by reduction of NSF2, of the apical determinant Crumbs, or of septate junction protein Varicose.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Genetic Complementation Test
  • Genotype
  • Germinal Center Kinases
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Mutation
  • N-Ethylmaleimide-Sensitive Proteins / genetics*
  • Phenotype
  • Protein-Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Sequence Homology, Amino Acid
  • Trachea / embryology*


  • Apoptosis Regulatory Proteins
  • CCM3 protein, Drosophila
  • Drosophila Proteins
  • Germinal Center Kinases
  • Membrane Proteins
  • Nsf2 protein, Drosophila
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • N-Ethylmaleimide-Sensitive Proteins