Sorting Robo Rather Than Clearing It

Science's STKE  08 Feb 2005:
Vol. 2005, Issue 270, pp. tw56
DOI: 10.1126/stke.2702005tw56

During development of the central nervous system, axons either cross or do not cross the midline, a decision that depends on whether their growth cones express the Slit receptor Roundabout (Robo): Robo expression leads to repulsion from the midline and failure to cross. In Drosophila, Commisureless (Comm), which is expressed in both midline cells and crossing neurons, regulates surface expression of Robo (and thereby midline crossing), but the specific mechanisms underlying this regulation--and in precisely which cells Comm expression is critical to Robo regulation--have been controversial (see Krull). Keleman et al. showed that, in flies that lacked comm, selective expression of comm in neurons that cross the midline in wild-type Drosophila substantially rescued midline crossing and that expressing comm in midline cells as well did not further promote axonal crossing. Mutations that interfered with Comm and Robo targeting to late endosomes and lysosomes when expressed in COS-7 cells specifically interfered with the ability of Comm to promote midline crossing in vivo. Further mutational analysis indicated that Comm ubiquitination was not required for its functional effects, as did genetic manipulation of the ubiquitin ligase Nedd4. Movies of green fluorescent protein-labeled Robo expressed in Drosophila peripheral neurons showed that Comm expression prevented anterograde axonal trafficking of Robo. Thus, Comm expression in crossing neurons but not midline cells is critical to its regulation of midline crossing, and Comm appears to regulate Robo surface expression by controlling its sorting at the Golgi rather than by promoting its removal from the plasma membrane.

K. Keleman, C. Ribeiro, B. J. Dickson, Comm function in commissural axon guidance: Cell-autonomous sorting of Robo in vivo. Nat. Neurosci. 8, 156-163 (2005). [PubMed]

C. E. Krull, Comm-ing across the midline. Nat. Neurosci. 8, 131-132 (2005). [PubMed]