A Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons.
The c-Jun N-terminal kinase (JNK) of the MAP kinase superfamily is activated in response to a variety of cellular stresses and is involved in apoptosis in neurons. However, the roles of the JNK signaling pathway in the nervous system are unknown. The genes for the Caenorhabditis elegans homolog of JNK, JNK-1, and its direct activator, JKK-1, were isolated based on their abilities to function in the Hog1 MAP kinase pathway in yeast. JKK-1 is a member of the MAP kinase kinase superfamily and functions as a specific activator of JNK. Both jnk-1 and jkk-1 are expressed in most neurons. jkk-1 null mutant animals exhibit defects in locomotion that can be rescued by the conditional expression of JKK-1 in mutant adults, suggesting that the defect is not due to a developmental error. Furthermore, ectopic expression of JKK-1 in type-D motor neurons is sufficient to rescue the movement defect. Thus, the C.elegans JNK pathway functions in type-D GABAergic motor neurons and thereby modulates coordinated locomotion.
Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan.
M
M
Kawasaki
N
N
Hisamoto
Y
Y
Iino
M
M
Yamamoto
J
J
Ninomiya-Tsuji
K
K
Matsumoto
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000201:enzymology; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D017353:Gene Deletion; D015870:Gene Expression; D005800:Genes, Fungal; D017238:Genes, Helminth; D005816:Genetic Complementation Test; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D009068:Movement; D010802:Phylogeny; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D005680:gamma-Aminobutyric Acid; D011494:Protein Kinases; C120814:jkk-1 protein, C elegans; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases