A potassium channel-MiRP complex controls neurosensory function in Caenorhabditis elegans.
MinK-related peptides (MiRPs) are single transmembrane proteins that associate with mammalian voltage-gated K(+) subunits. Here we report the cloning and functional characterization of a MiRP beta-subunit, MPS-1, and of a voltage-gated pore-forming potassium subunit, KVS-1, from the nematode Caenorhabditis elegans. mps-1 is expressed in chemosensory and mechanosensory neurons and co-localizes with kvs-1 in a subset of these. Inactivation of either mps-1 or kvs-1 by RNA interference (RNAi) causes partially overlapping neuronal defects and results in broad-spectrum neuronal dysfunction, including defective chemotaxis, disrupted mechanotransduction, and impaired locomotion. Inactivation of one subunit by RNAi dramatically suppresses the expression of the partner subunit only in cells where the two proteins co-localize. Co-expression of MPS-1 and KVS-1 in mammalian cells gives rise to a potassium current distinct from the KVS-1 current. Taken together these data indicate that potassium currents constitute a basic determinant for C. elegans neuronal function and unravel a unifying principle of evolutionary significance: that potassium channels in various organisms use MiRPs to generate uniqueness of function with rich variation in the details.
Bianchi
Laura
L
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Kwok
Suk-Mei
SM
Driscoll
Monica
M
Sesti
Federico
F
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D019143:Evolution, Molecular; D014644:Genetic Variation; D008124:Locomotion / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology; D009490:Neurosecretory Systems / Q000166:cytology / Q000502:physiology*; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D017434:Protein Structure, Tertiary; D051672:Shal Potassium Channels; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; C473893:MPS-1 protein, C elegans; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; C059983:potassium channel protein I(sk)