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The highly conserved cochaperone DnaJ/Hsp40 family proteins are known to interact with molecular chaperone Hsp70, and can regulate many cellular processes including protein folding, translocation, and degradation. In studies of Caenorhabditis elegans locomotion mutants, we identified a gain-of-function (gf) mutation in dnj-17 closely linked to the widely used e156 null allele of C. elegans GAD (glutamic acid decarboxylase) unc-25 dnj-17 encodes a DnaJ protein orthologous to human DNAJA5. In C. elegans DNJ-17 is a cytosolic protein and is broadly expressed in many tissues. dnj-17(gf) causes a single amino acid substitution in a conserved domain, and behaves as a hypermorphic mutation. The effect of this dnj-17(gf) is most prominent in mutants lacking GABA synaptic transmission. In a seizure model caused by a mutation in the ionotropic acetylcholine receptor acr-2(gf), dnj-17(gf) exacerbates the convulsion phenotype in conjunction with absence of GABA. Null mutants of dnj-17 show mild resistance to aldicarb, while dnj-17(gf) is hypersensitive. These results highlight the importance of DnaJ proteins in regulation of C. elegans locomotor circuit, and provide insights into the in vivo roles of DnaJ proteins in humans., (Copyright © 2016 Takayanagi-Kiya and Jin.)

DjB1 (Hsp40/DnajB1/Hdj1) is a member of the Hsp40/DnaJ family that functions as a co-chaperone of mammalian Hsp70s. DjB1 recognizes substrate proteins and facilitates the ATPase activity of Hsp70. We generated DjB1 deficient mice. The DjB1(-/-) mice were viable and fertile with no obvious abnormalities, thus indicating that DjB1 is dispensable for development and viability. No difference was found between the DjB1(-/-) and wild-type peritoneal macrophages regarding resistance against various types of apoptosis-inducing reagents. However, DjB1(-/-) cells showed decreased thermotolerance in the early phase after mild heat treatment, but not in the late phase. After the heat treatment, Hsp70 was induced similarly in wild-type and DjB1(-/-) cells. Immunofluorescence staining of wild-type cells revealed the accumulation of DjB1 and Hsc70 in the nucleus after heat treatment. DjB1 also accumulated in the centrosome. The accumulation of Hsc70 in the nucleus was also observed in DjB1(-/-) cells. These results suggest that the impaired thermotolerance of DjB1(-/-) cells is not due to a mislocation of the Hsp70 family.