title: Regulators of the actin cytoskeleton mediate lethality in a Caenorhabditis elegans dhc-1 mutant.
abstract: Functional analysis of cytoplasmic dynein in Caenorhabditis elegans has revealed a wide range of cellular functions for this minus-end-directed motor protein. Dynein transports a variety of cargos to diverse cellular locations, and thus cargo selection and destination are likely regulated by accessory proteins. The microtubule-associated proteins LIS-1 and dynein interact, but the nature of this interaction remains poorly understood. Here we show that both LIS-1 and the dynein heavy-chain DHC-1 are required for integrity of the actin cytoskeleton in C. elegans. Although both dhc-1(or195ts) and lis-1 loss-of-function disrupt the actin cytoskeleton and produce embryonic lethality, a double mutant suppresses these defects. A targeted RNA interference screen revealed that knockdown of other actin regulators, including actin-capping protein genes and prefoldin subunit genes, suppresses dhc-1(or195ts)-induced lethality. We propose that release or relocation of the mutant dynein complex mediates this suppression of dhc-1(or195ts)-induced phenotypes. These results reveal an unexpected direct or indirect interaction between the actin cytoskeleton and dynein activity.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Aleksandra J
authors.initials: AJ
authors.lastname: Gil-Krzewska
authors.forename: Erica
authors.initials: E
authors.lastname: Farber
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Buttner
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hunter
mesh_terms: D000199:Actins / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology; D004398:Dyneins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D016153:Genes, Suppressor; D006066:Gonads / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D049471:Pachytene Stage / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference / Q000187:drug effects; D013489:Suppression, Genetic / Q000187:drug effects
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; D047630:Depsipeptides; D008869:Microtubule-Associated Proteins; C513193:lis-1 protein, C elegans; C057531:jasplakinolide; D056445:Cytoplasmic Dyneins; C502824:DHC-1 protein, C elegans; D004398:Dyneins