Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin, an activator of adenylate cyclase, stimulates motility in molluscan gill cilia and sperm flagella. To determine and compare potential targets of cAMP action, dynein was prepared from the lateral gill.cilia and sperm flagella of the mussel Mytilus edulis and the clam Spisula solidissima. In the flagella of both species, high-salt extraction removes about half of the ATPase activity, half of the alpha and beta heavy chains, and the outer arms. The dynein from both species sediments at 18-20 S, contains two or three intermediate chains, and three light chains. High-salt plus detergent removes most of the remaining dynein ATPase, alpha and beta heavy chains, and inner arms, also yielding a stable 18-20 S particle. In gill cilia of both species, high-salt extraction removes only 12-18% of the ATPase, up to 1/3 of the alpha heavy chains, an equivalent amount of beta heavy chain, and a subset of the outer arms. The dynein sediments at 18-20 S and, in Spisula, the heavy, intermediate, and light chains precisely co-sediment. High-salt plus detergent removes another 1/3 of the alpha heavy chains, an equivalent amount of beta heavy chain, and the remaining outer arms. The ATPase sediments mainly as a 13-14 S form showing considerable dissociation of co-sedimenting intermediate and light chains. The inner arms and at least half of the ciliary dynein ATPase activity remain unextractable, corresponding in mass mainly to an apparent beta heavy chain that is vanadate-cleavable. Cyclic AMP-dependent, calcium-independent phosphorylation takes place on specific dynein light chains in cilia but on only the dynein alpha heavy chain in flagella. Pre-activation of the flagella prevents subsequent addition of labeled phosphate. Phosphorylation has no effect on the steady-state ATPase properties. The single phosphate added to the flagellar alpha chain is located within the LUV1 vanadate photocleavage fragment. Considering the probable locus of the light chains and the site of the alpha heavy chain phosphorylation, both beyond the active site and toward the base of the molecule, these distinct phosphorylations may regulate dynein action by modulating arm flexibility or interaction.
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PMID:Dynein from serotonin-activated cilia and flagella: extraction characteristics and distinct sites for cAMP-dependent protein phosphorylation. 148 8

Lateral (L) cilia of Mytilus gill are activated by serotonin which, in molluscan systems, is known to activate adenylate cyclase. Triton-extracted models of L-cells, arrested at greater than 10(-6) M Ca++, are stimulated to beat by the addition of 10(-5) M cAMP while still under Ca++ arrest conditions, suggesting that cAMP-activation is not mediated by alterations of Ca++ levels. Using isolated, permeabilized cilia, we find, independent of [Ca++], that cAMP-dependent protein phosphorylation in L-cilia occurs uniquely and reversibly on three low molecular weight polypeptides of 23,000, 18,000, and 14,000 daltons. Phosphorylation is maximal at cAMP concentrations above 0.5 microM. The phosphorylated chains partially co-extract at high salt with a 14S dynein fraction and have approximately the same molecular weights as reported for dynein light chains. Such conditions mainly extract the outer dynein arm, about 40% of the Mg++-ATPase activity, and a corresponding amount of the cAMP phosphorylated chains. However, the three polypeptides sediment together at 10-11S, clearly separable from the 14S dynein ATPase. Using a gel-overlay technique, we find that calmodulin binds to axonemal polypeptides of L-cilia with molecular weights of 18,000 and 13,000, independent of Ca++, while in mixed-population cilia, only a 12,000 dalton chain binds calmodulin, in a Ca++ dependent manner. In neither case are calmodulin binding proteins found in the high salt fraction containing the cAMP-dependent phosphorylated chains, indicating that, in spite of some similarity in molecular weight, the cAMP-phosphorylated and calmodulin binding polypeptides are different. Also, double-labelling indicates that only the 18,000 dalton chains co-migrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP and calcium in the differential control of Mytilus gill cilia. 301 53

The sliding-tubule hypothesis of flagellar movement has strong experimental support, but our present knowledge of the mechanism by which this sliding is coordinated and converted into flagellar oscillation and bend propagation is quite limited. Among the few facts known are: (1) calcium has a role in regulating the asymmetry of flagellar waveform, (2) the initiation or activation of motility in spermatozoa from several species involves a cyclic AMP-dependent phosphorylation reaction, and (3) the conversion of tubule sliding to bending does not require the radial spokes or central tubules. Inhibitors are valuable tools for investigating mechanisms involved in cellular function, and we report here that Li+ in low concentrations reversibly inhibits the microtubule-based movement of reactivated sea urchin sperm flagella. The evidence indicates that the action of Li+ is directed primarily towards one or more regulatory sites through which Ca2+ modulates the asymmetry of flagellar waveform, rather than towards dynein ATPase itself. Lithium also appears to inhibit the sperm adenylate cyclase, but this action does not seem to be relevant to its inhibition of normal motility. Our findings indicate the need for considerable caution when using ATP analogues supplied as the Li+ salt.
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PMID:Lithium reversibly inhibits microtubule-based motility in sperm flagella. 672 11