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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Gene Review

comm  -  commissureless

Drosophila melanogaster

Synonyms: CG17943, Comm, Dmel\CG17943, Protein commissureless
 
 
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High impact information on comm

  • It has also been suggested that Comm must be ubiquitinated by the Nedd4 ubiquitin ligase [1].
  • Two different models have been proposed for how Comm regulates Robo: a 'sorting' model and a 'clearance' model, both based on studies using heterologous cells in vitro [1].
  • We show that Commissureless binds to and is regulated by the ubiquitin ligase DNedd4 [2].
  • commissureless and roundabout lead to complementary mutant phenotypes in which either too few or too many axons cross the midline [3].
  • Here, we report on the molecular cloning, characterization, and expression of the comm gene. comm encodes a novel protein of 370 amino acids that lacks a signal sequence, has a transmembrane domain, and biochemically copurifies with membranes [4].
 

Biological context of comm

  • We have found that expression of Comm in the midline cells is unable to rescue the comm phenotype and that tagged versions of Comm are not transferred to axons [5].
  • Furthermore, specific expression of an elav transgene in posterior neurons of each segment of an elav mutant nerve cord restores comm mRNA expression in these cells, as well as the formation of posterior commissures [6].
  • A re-examination of Comm protein expression and the use of targeted RNA interference reveal that correct midline crossing requires that Comm is expressed in the commissural axons and midline glia [5].
  • These results demonstrate that dNedd4 and ubiquitination are required for Commissureless endocytosis and proper neuromuscular synaptogenesis [7].
  • Expression of the Comm mutants later in muscle development, after synaptic innervation, has no effect [7].
 

Anatomical context of comm

  • In the nerve cord of elav mutant embryos, comm mRNA expression is strongly reduced in neurons, but not in midline glial cells [6].
  • In the absence of Commissureless (Comm) function, axons are unable to extend across the central nervous system midline [5].
  • Mutations in comm lead to an absence of nearly all CNS axon commissures, such that growth cones that normally project across the midline instead now extend only on their own side [8].
  • Thus, synaptogenesis initiation is positively correlated with endocytosis of COMM in postsynaptic muscle cells [9].
 

Physical interactions of comm

  • Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly, there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif [10].
 

Regulatory relationships of comm

 

Other interactions of comm

  • Here we show that the Rptp mutations genetically interact with robo, slit and comm [11].
  • We show here, however, that ubiquitination of Comm is not required for its function in vitro or in vivo, and that Nedd4 is unlikely to function in axon guidance at the midline [1].
  • Regulation of Commissureless by the Ubiquitin Ligase DNedd4 Is Required for Neuromuscular Synaptogenesis in Drosophila melanogaster [7].
  • In comm mutants, where repulsive signals remain elevated, increasing or decreasing Abl activity partially rescues commissure formation [13].
  • The actual molecular characterization of the Shaker locus is already under way (cf. Jan et al., this volume; M. Tanouye , pers. comm .) [14].
 

Analytical, diagnostic and therapeutic context of comm

  • Axotomy could overturn the normal polarity of the RP motoneurons in favor of the development of an ipsilateral motor axon, and this reversed morphology was also observed when the motor axon could not extend across the midline in the commissureless mutant [15].

References

  1. Comm function in commissural axon guidance: cell-autonomous sorting of Robo in vivo. Keleman, K., Ribeiro, C., Dickson, B.J. Nat. Neurosci. (2005) [Pubmed]
  2. Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Myat, A., Henry, P., McCabe, V., Flintoft, L., Rotin, D., Tear, G. Neuron (2002) [Pubmed]
  3. Dosage-sensitive and complementary functions of roundabout and commissureless control axon crossing of the CNS midline. Kidd, T., Russell, C., Goodman, C.S., Tear, G. Neuron (1998) [Pubmed]
  4. commissureless controls growth cone guidance across the CNS midline in Drosophila and encodes a novel membrane protein. Tear, G., Harris, R., Sutaria, S., Kilomanski, K., Goodman, C.S., Seeger, M.A. Neuron (1996) [Pubmed]
  5. Commissureless is required both in commissural neurones and midline cells for axon guidance across the midline. Georgiou, M., Tear, G. Development (2002) [Pubmed]
  6. The Drosophila RNA-binding protein ELAV is required for commissural axon midline crossing via control of commissureless mRNA expression in neurons. Simionato, E., Barrios, N., Duloquin, L., Boissonneau, E., Lecorre, P., Agn??s, F. Dev. Biol. (2007) [Pubmed]
  7. Regulation of Commissureless by the Ubiquitin Ligase DNedd4 Is Required for Neuromuscular Synaptogenesis in Drosophila melanogaster. Ing, B., Shteiman-Kotler, A., Castelli, M., Henry, P., Pak, Y., Stewart, B., Boulianne, G.L., Rotin, D. Mol. Cell. Biol. (2007) [Pubmed]
  8. Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Seeger, M., Tear, G., Ferres-Marco, D., Goodman, C.S. Neuron (1993) [Pubmed]
  9. Commissureless endocytosis is correlated with initiation of neuromuscular synaptogenesis. Wolf, B., Seeger, M.A., Chiba, A. Development (1998) [Pubmed]
  10. Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. Kanelis, V., Bruce, M.C., Skrynnikov, N.R., Rotin, D., Forman-Kay, J.D. Structure (2006) [Pubmed]
  11. Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo. Sun, Q., Bahri, S., Schmid, A., Chia, W., Zinn, K. Development (2000) [Pubmed]
  12. Calmodulin and son of sevenless dependent signaling pathways regulate midline crossing of axons in the Drosophila CNS. Fritz, J.L., VanBerkum, M.F. Development (2000) [Pubmed]
  13. Abelson tyrosine kinase is required to transduce midline repulsive cues. Hsouna, A., Kim, Y.S., VanBerkum, M.F. J. Neurobiol. (2003) [Pubmed]
  14. Genetic and voltage-clamp analysis of a Drosophila potassium channel. Salkoff, L. Cold Spring Harb. Symp. Quant. Biol. (1983) [Pubmed]
  15. Development of a polar morphology by identified embryonic motoneurons. Whitington, P.M., Sink, H. Int. J. Dev. Neurosci. (2004) [Pubmed]
 
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