Arellano-Carbajal, Fausto; Briseño-Roa, Luis; Couto, Africa; Cheung, Benny H. H.; Labouesse, Michel; de Bono, MarioISTA
Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O2 responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca2+ transients, at least in some neurons: in maco-1 mutants the O2-sensing neuron PQR is unable to generate a Ca2+ response to a rise in O2. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O2, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca2+ channels, also fails to disrupt Ca2+ responses in the PQR cell body to O2 stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca2+ channel α1 subunit, recapitulate the Ca2+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or traffic of ion channels or ion channel regulators.
Arellano-Carbajal F, Briseño-Roa L, Couto A, Cheung BHH, Labouesse M, de Bono M. Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability. PLoS Genetics. 2011;7(3). doi:10.1371/journal.pgen.1001341
Arellano-Carbajal, F., Briseño-Roa, L., Couto, A., Cheung, B. H. H., Labouesse, M., & de Bono, M. (2011). Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1001341
Arellano-Carbajal, Fausto, Luis Briseño-Roa, Africa Couto, Benny H. H. Cheung, Michel Labouesse, and Mario de Bono. “Macoilin, a Conserved Nervous System–Specific ER Membrane Protein That Regulates Neuronal Excitability.” PLoS Genetics. Public Library of Science, 2011. https://doi.org/10.1371/journal.pgen.1001341.
F. Arellano-Carbajal, L. Briseño-Roa, A. Couto, B. H. H. Cheung, M. Labouesse, and M. de Bono, “Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability,” PLoS Genetics, vol. 7, no. 3. Public Library of Science, 2011.
Arellano-Carbajal F, Briseño-Roa L, Couto A, Cheung BHH, Labouesse M, de Bono M. 2011. Macoilin, a conserved nervous system–specific ER membrane protein that regulates neuronal excitability. PLoS Genetics. 7(3), e1001341.
Arellano-Carbajal, Fausto, et al. “Macoilin, a Conserved Nervous System–Specific ER Membrane Protein That Regulates Neuronal Excitability.” PLoS Genetics, vol. 7, no. 3, e1001341, Public Library of Science, 2011, doi:10.1371/journal.pgen.1001341.
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