Creutzfeldt‐Jakob infection increases adenylate cyclase activity in specific regions of guinea pig brain

Rasenick, Mark M.; Valley, Susan; Manuelidis, Elias E.; Manuelidis, Laura

doi:10.1016/0014-5793(86)81205-4

Cited by 11 publications

(5 citation statements)

References 22 publications

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“…Several studies have proposed that there is some interaction between cytoskeletal components and the adenylate cyclase system (see Zor, 1983, andRasenick et al, 1986, for reviews). Adenylate cyclase activity appears to copolymerize with microtubules (Margolis and Wilson, 1979;Wolff and Cook, 1985), and Gs has been observed to associate with cytoskeletal components (Sahyoun et al, 198 1;Rasenick, 1986) as has Gi (Higashi and Ishibashi, 1985).…”

Section: Discussionmentioning

confidence: 99%

Exchange of Guanine Nucleotides Between Tubulin and GTP‐Binding Proteins That Regulate Adenylate Cyclase: Cytoskeletal Modification of Neuronal Signal Transduction

Rasenick¹,

Wang²

1988

Journal of Neurochemistry

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Tubulin, the primary constituent of microtubules, is a GTP-binding proteins with structural similarities to other GTP-binding proteins. Whereas microtubules have been implicated as modulators of the adenylate cyclase system, the mechanism of this regulation has been elusive. Tubulin, polymerized with the hydrolysis-resistant GTP analog, 5'-guanylylimidodiphosphate [Gpp(NH)p], can promote inhibition of synaptic membrane adenylate cyclase which persists subsequent to washing. Tubulin with Gpp(NH)p bound was slightly less potent than free Gpp(NH)p in the inhibition of adenylate cyclase, but tubulin without nucleotide bound had no effect on the enzyme. A GTP-binding protein from the rod outer segment (transducin), with Gpp(NH)p bound, was also without effect on adenylate cyclase. Tubulin (regardless of the nucleotide bound to it) did not alter the activity of the adenylate cyclase catalytic unit directly. When tubulin was polymerized with the hydrolysis-resistant photoaffinity GTP analog, [32P]P3(4-azidoanilido)-P1-5'-GTP ([32P]AAGTP), and this protein was added to synaptic membranes, AAGTP was transferred from tubulin to the inhibitory GTP-binding protein, Gi. This transfer was blocked by prior incubation of the membranes with Gpp(NH)p or covalent binding of AAGTP to tubulin prior to exposure of that tubulin to membranes. Incubation of membranes with Gpp(NH)p subsequent to incubation with tubulin-AAGTP results in a decrease in AAGTP bound to Gi and a compensatory increase in AAGTP bound to the stimulatory GTP-binding protein, Gs. Likewise, persistent inhibition of adenylate cyclase by tubulin-Gpp(NH)p could be overridden by the inclusion of 100 microM Gpp(NH)p in the assay inhibition. Whereas Gpp(NH)p promotes persistent inhibition of synaptic membrane adenylate cyclase without incubation at elevated temperatures, tubulin [with AAGTP or Gpp(NH)p bound] requires 30 s incubation at 23 degrees C to effect adenylate cyclase inhibition. Photoaffinity experiments yield parallel results. These data are consistent with synaptic membrane tubulin regulating neuronal adenylate cyclase by transferring GTP to Gi and, subsequently, to Gs.

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Section: Discussionmentioning

confidence: 99%

Exchange of Guanine Nucleotides Between Tubulin and GTP‐Binding Proteins That Regulate Adenylate Cyclase: Cytoskeletal Modification of Neuronal Signal Transduction

Rasenick¹,

Wang²

1988

Journal of Neurochemistry

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“…Only more rigorous purification of infectivity will permit the unambiguous detections of integral agent peptides that are likely to be more minor than those described here. On a functional level, however, some of the major peptides here described (i.e., Gp34) may also play a role in physiologically relevant membrane changes, such as the increased synaptic adenylate cyclase activity seen in CJD (29).…”

Section: Discussionmentioning

confidence: 99%

Characterization of major peptides in Creutzfeldt-Jakob disease and scrapie.

Sklaviadis¹,

Manuelidis²,

Manuelidis³

1986

Proc. Natl. Acad. Sci. U.S.A.

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In Creutzfeldt-Jakob disease three major peptides cosedinient with the infectious agent. These distinct peptides are not present in identical fractions from uninfected brain, and bind to polyclonal antibodies raised against "prion protein" purified by protease treatment. Three similar distinct peptides are also found in scrapie-infected brain fractions purified without the use of proteases. To clarify the relationships between these distinct peptides and prion protein, peptides were analyzed on immunoblots after cleavage with various glycosidases. (2,(7)(8)(9). Previous studies suggested PrP could be partially or completely derived from a 33-to 35-kDa peptide (2, 10). The PrP nucleotide sequence, which was identified using a synthetic oligonucleotide (10), is found in the host genome. PrP mRNA is present in equivalent amounts in both normal and infected tissues (10, 11). We thus sought to further characterize the major peptides in nonprotease-treated CJD infectious fractions (i) to further clarify the origin of PrP, (ii) to determine the nature of the glycosylation on major peptides, and (iii) to resolve the question of peptide heterogeneity in infectious fractions. With glycosidase treatments and nonequilibrium pH gradient electrophoresis (NEPHGE) it was possible to determine the sugar residues on each distinct peptide species ahd to clearly delineate heterogeneous, peptides that cosediment with the infectious agent. These analyses suggest that the identified PrP sequence may be but one of several major feptide species that cosediment with the CJD and scrapie agents. MATERIALS AND METHODSThe 215,000 x g salt pellet (p215s), which conltains high yields of the infectious agent (2), was derived from CJD infected hamster brains (12) with the addition of 0.05% (vol/vol) diisopropylfluorophosphate and 0.5 mM phenylmethylsulfonyl fluoride. Some p215s pellets were resuspended and treated with proteinase K (2, 13). Similarly prepared 263K scrapie p215s fractions were a generous gift of R. Rubinstein. Proteins were blotted from NaDodSO4/polyacrylamide gels (2) and reacted with biotinylated lectins or anti-scrapie antibodies as described (2), except that goat anti-rabbit alkaline phosphatase (1:1000 dilution, Tago) was used to detect antibodies. Neuraminidase (0.5 unit/ml, Calbiochem) digestions were done in 25 mM sodium acetate (pH 5.5), 2 mM CaC12, 77 mM NaCl at 370C for 24 hr (14,15 6146The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…Sc -infected brains, of the levels of serotonin, dopamine, and norepinephrine (25)(26)(27), as well as in the activity of monoaminergic receptors (28) and related enzymes, such as monoaminooxidase B (29) and adenylyl cyclase (30). Moreover, serotonergic dysfunction was observed in human clinical cases of fatal familial insomnia (31), and dopaminergic depletion was reported in patients with CreutzfeldtJakob disease, associated with rapid cognitive decline and movement disorders (32,33).…”

Section: Changes Were Reported In Prpmentioning

confidence: 99%

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

Beckman

Santos

Americo

et al. 2015

Journal of Biological Chemistry

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Background:The prion protein (PrP C ) functions as a scaffold for cell surface signaling systems, and plays a role in neurodegenerative diseases that include clinical depression among their symptoms. Results: PrP C -null mice showed depressive-like behavior concomitant with functional changes in monoaminergic systems. Conclusion: PrP C regulates functions of monoaminergic synapses. Significance: PrP C may be involved in major depression and related neuropsychiatric disorders.

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Creutzfeldt‐Jakob infection increases adenylate cyclase activity in specific regions of guinea pig brain

Cited by 11 publications

References 22 publications

Exchange of Guanine Nucleotides Between Tubulin and GTP‐Binding Proteins That Regulate Adenylate Cyclase: Cytoskeletal Modification of Neuronal Signal Transduction

Exchange of Guanine Nucleotides Between Tubulin and GTP‐Binding Proteins That Regulate Adenylate Cyclase: Cytoskeletal Modification of Neuronal Signal Transduction

Characterization of major peptides in Creutzfeldt-Jakob disease and scrapie.

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

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