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jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans.


Villanueva, A; Lozano, J; Morales, A; Lin, X; Deng, X; Hengartner, M O; Kolesnick, R N (2001). jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans. The EMBO Journal, 20(18):5114-5128.

Abstract

Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK, jnk-1, and two MKK-7s, mek-1 and jkk-1, were cloned. Here we characterize jnk-1, which encodes two isoforms JNK-1 alpha and JNK-1 beta. A null allele, jnk-1(gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to jkk-1 mutants, elimination of GABAergic signals suppressed the jnk-1(gk7) locomotion defect. Like mek-1 nulls, jnk-1(gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While jkk-1 or mek-1 inactivation mimicked jnk-1(gk7) locomotion and heavy metal stress defects, respectively, mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through jkk-1 and mek-1 in C.elegans, and define interaction between MKK7, but not MKK4, and JNK.

Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK, jnk-1, and two MKK-7s, mek-1 and jkk-1, were cloned. Here we characterize jnk-1, which encodes two isoforms JNK-1 alpha and JNK-1 beta. A null allele, jnk-1(gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to jkk-1 mutants, elimination of GABAergic signals suppressed the jnk-1(gk7) locomotion defect. Like mek-1 nulls, jnk-1(gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While jkk-1 or mek-1 inactivation mimicked jnk-1(gk7) locomotion and heavy metal stress defects, respectively, mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through jkk-1 and mek-1 in C.elegans, and define interaction between MKK7, but not MKK4, and JNK.

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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:17 September 2001
Deposited On:11 Feb 2008 12:19
Last Modified:05 Apr 2016 12:16
Publisher:European Molecular Biology Organization ; Nature Publishing Group
ISSN:0261-4189
Publisher DOI:10.1093/emboj/20.18.5114
PubMed ID:11566876
Permanent URL: http://doi.org/10.5167/uzh-960

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