Disease relevance of Dnajc5

• We found that: (1) HeLa cells, 2 esophageal cancer lines, rat 3Y1 fibroblasts transformed by either adenovirus type 12, mouse polyoma virus, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene all formed colonies on CSP and in agar and at the same time was tumorigenic [1].

High impact information on Dnajc5

• Cysteine string protein immunoreactivity in the nervous system and adrenal gland of rat [2].
• Csp immunoreactivity is particularly abundant in synapse-rich regions including those of the retina, main olfactory bulb, hippocampal formation, and cerebellum [2].
• In this report, we demonstrate that CSP selectively interacts with G alpha(s) and increases steady-state GTP hydrolysis [3].
• Furthermore, transient expression of CSP in HEK cells increased cellular cAMP levels in the presence of the beta2 adrenergic agonist isoproterenol [3].
• Cysteine string protein (CSP), a 34-kDa molecular chaperone, is expressed on synaptic vesicles in neurons and on secretory vesicles in endocrine, neuroendocrine, and exocrine cells [4].

Biological context of Dnajc5

• Phosphorylation of cysteine string protein in the brain: developmental, regional and synaptic specificity [5].
• Genetic studies have implicated each of these proteins in the Ca2+-dependency of exocytosis and, since CSP does not bind Ca2+, this novel interaction might explain the Ca2+-dependent actions of CSP [6].
• A Csp binding site on the P/Q-type calcium channel is thus located within the 200 residue synaptic protein interaction site that can also bind syntaxin I, SNAP-25, and synaptotagmin I [7].
• Cysteine-string protein in inner hair cells of the organ of Corti: synaptic expression and upregulation at the onset of hearing [8].
• CSP function is vital to synaptic transmission, however; the precise nature of its role remains controversial [9].

Anatomical context of Dnajc5

• Immunohistochemical analysis of the cerebellar cortex revealed a novel pool of P-CSP that did not colocalize with synaptic vesicle markers during early development [5].
• Phosphorylation-dependent interaction of the synaptic vesicle proteins cysteine string protein and synaptotagmin I [6].
• Complexes containing CSP and synaptotagmin were immunoprecipitated from rat brain membranes, further suggesting that these proteins interact in vivo [6].
• Cysteine string protein, a DnaJ family member, is present on diverse secretory vesicles [10].
• In developmental studies in the rat, we observed that cysteine-string protein was present beneath the inner hair cells at birth and beneath outer hair cells by postnatal day 2 only [8].

Associations of Dnajc5 with chemical compounds

• A rat brain complementary DNA (cDNA) encoding CSP was isolated and sequence analysis predicts a protein with 86% identity to Torpedo CSP [10].
• In conclusion, the close association of cysteine-string protein with synaptic vesicles tethered to synaptic ribbons in inner hair cells and its synchronized expression with the appearance and maturation of the cochlear potentials strongly suggest that this protein plays a fundamental role in sound-evoked glutamate release by inner hair cells [8].
• In the present study, reverse transcription-polymerase chain reaction analysis confirmed the induction of CSP at mRNA levels in rat frontal cortex after chronic treatment with two different classes of antidepressants, imipramine or sertraline [11].
• Changes in mRNA levels for heat-shock/stress proteins (Hsp) and a secretory vesicle associated cysteine-string protein (Csp1) after amphetamine (AMPH) exposure [12].
• Here we have examined the effects of huntingtin fragments (exon 1) with (huntingtin(exon1/exp)) and without (huntingtin(exon1/nonexp)) expanded polyglutamine (polyQ) tracts on the CSP chaperone system [4].

Physical interactions of Dnajc5

• Binding assays in vitro using recombinant proteins confirmed a direct interaction between the two proteins and demonstrated that the PKA-phosphorylated form of CSP binds synaptotagmin with approximately an order of magnitude lower affinity than the non-phosphorylated form [6].

Other interactions of Dnajc5

• Furthermore, pull-down assays using cAMP-dependent protein kinase (PKA)-phosphorylated CSP recovered significantly less synaptotagmin [6].
• Synaptotagmin was detected in channel-associated complexes, but not synaptophysin, Rab 3A nor rat cysteine string protein [13].
• The N-terminal binding site of CSP, which includes the J domain, binds Galpha subunits but not Galphabeta subunits whereas the C terminal binding site of CSP associates with either free Galphabeta subunits or Galphabeta in complex with Galpha [14].
• Munc-18-1 and cysteine string protein (csp) in pinealocytes of the gerbil pineal gland [15].

Analytical, diagnostic and therapeutic context of Dnajc5

• Western blotting revealed that the proportion of phosphorylated CSP (P-CSP) varies between distinct brain regions and also exhibits developmental regulation, with P-CSP highest early in development [5].
• Here we have examined the self-association of CSP to form oligomers that are stable upon SDS-PAGE [9].
• RT-PCR products for Csp1 were produced in total RNA obtained from brain but not from cultured astrocytes, suggesting that the Csp1 mRNA measured by RT-PCR is of neuronal origin [12].
• To study this issue, we analyzed the effects of chronic lithium administration (21 days) on csp mRNA levels in rat brain using in situ hybridization [16].
• In this context, we observed recently that lithium at therapeutically relevant concentrations enhanced expression of cysteine string protein (csp) at the level of both mRNA and protein, in cell culture and in rat brain [16].

References