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8.A.38 The Animal Macoilin Regulator of Ion Channels (Macoilin) Family

Macoilins have four-five conserved N-terminal predicted TMSs and C-terminally coiled-coil regions. They are found throughout Eumetazoa but not in other organisms. Mutants for the single C. 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. Arellano-Carbajal et al. (2011) showed 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. 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 seen in MACO-1 mutants. Thus, macoilin acts in the ER to regulate assembly or traffic of ion channels.

References associated with 8.A.38 family:

Arellano-Carbajal, F., L. Briseño-Roa, A. Couto, B.H. Cheung, M. Labouesse, and M. de Bono. (2011). Macoilin, a conserved nervous system-specific ER membrane protein that regulates neuronal excitability. PLoS Genet 7: e1001341. 21437263