Macoilin: an ER Protein Regulating Neuron Activity Figure 6. maco-1 mutants have subtle synaptic morphology defects. SNB-1::GFP puncta along the ventral (A) and dorsal (C) nerve cords of wild type and maco-1(db9) mutants. (B, D) Quantification of SNB-1::GFP puncta number and area in wild type and maco-1 mutants in ventral (B) and dorsal (D) cords. (E, G) UNC-10::GFP puncta along the ventral (E) and dorsal (G) nerve cords of wild type and maco-1(db9) mutants. (F, H) Quantification of UNC-10::GFP puncta number and area in wild type and maco-1 mutants in ventral (F) and dorsal (H) cords. (I, K) SYD-2::GFP puncta in the ventral (I) and dorsal (K) nerve cords of wild type and maco-1 mutants. (J, L) Quantification of SYD-2::GFP puncta number and area in the ventral (J) and dorsal (L) cords of wild type and maco-1 mutants. The transgenic arrays used are: SNB-1::GFP (juIs1), SYD-2::GFP (hpIs3) and UNC-10::GFP (hpls61). Puncta analysis focussed on a 100 mm interval between motorneurons VD10 and VD12. All images are of 1-day-old adult hermaphrodites. Numbers are mean 6 s.e.m. Scale bar, 10 mm. * p,0.05, **p,0.01. doi:10.1371/journal.pgen.1001341.g006 Discussion Macoilins are a conserved family of multipass transmembrane proteins whose function has been mysterious. Members of the family can be found in eukaryotes that have a recognizable nervous system, from placozoa to humans, but not in yeast or Dictyostelium. Macoilins are expressed broadly but specifically in the nervous system. C. elegans macoilin is absent from neurites and is localized to the RER suggesting that it is involved in folding, assembly, or traffic of secreted or transmembrane proteins. The structure of macoilin contains two conserved regions: an N- terminal part that includes multiple transmembrane domains, and PLoS Genetics | www.plosgenetics.org 8 March 2011 | Volume 7 | Issue 3 | e1001341