Adenylyl cyclases from Plasmodium, Paramecium and Tetrahymena are novel ion channel/enzyme fusion proteins

Weber, Jost; Vishnyakov, Andrey E.; Hambach, Kristina; Schultz, Anita; Schultz, Joachim E.; Linder, Jürgen

doi:10.1016/s0898-6568(03)00129-3

Cited by 76 publications

(83 citation statements)

References 37 publications

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“…Structurally related cyclases have been characterized from M. tuberculosis and protozoans, but these are not thought to be G protein regulated. 37,48 Interestingly, the M. tuberculosis tmAC-like cyclase is analogous to half of a mammalian tmAC; it consists of a single six transmembrane helices domain followed by a cytoplasmic loop and has to homodimerize for activity. 37 Fungal ACs, although they occupy a separate branch of the nucleotidyl cyclase family tree (Figure 3), appear to combine features found in both tmACs and sAC.…”

Section: Evolution Of Mammalian Adenylyl Cyclasesmentioning

confidence: 99%

Molecular Details of cAMP Generation in Mammalian Cells: A Tale of Two Systems

Kamenetsky

Middelhaufe

Bank

et al. 2006

Journal of Molecular Biology

293

340

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The second messenger cAMP has been extensively studied for half a century, but the plethora of regulatory mechanisms controlling cAMP synthesis in mammalian cells is just beginning to be revealed. In mammalian cells, cAMP is produced by two evolutionary related families of adenylyl cyclases, soluble adenylyl cyclases (sAC) and transmembrane adenylyl cyclases (tmAC). These two enzyme families serve distinct physiological functions. They share a conserved overall architecture in their catalytic domains and a common catalytic mechanism, but they differ in their sub-cellular localizations and responses to various regulators. The major regulators of tmACs are heterotrimeric G proteins, which transduce extracellular signals via G protein-coupled receptors. sAC enzymes, in contrast, are regulated by the intracellular signaling molecules bicarbonate and calcium. Here, we discuss and compare the biochemical, structural and regulatory characteristics of the two mammalian AC families. This comparison reveals the mechanisms underlying their different properties but also illustrates many unifying themes for these evolutionary related signaling enzymes.

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Section: Evolution Of Mammalian Adenylyl Cyclasesmentioning

confidence: 99%

Molecular Details of cAMP Generation in Mammalian Cells: A Tale of Two Systems

Kamenetsky

Middelhaufe

Bank

et al. 2006

Journal of Molecular Biology

293

340

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“…Typically, ACs are highly specific for ATP with no detectable activity with GTP (Coudart-Cavalli et al 1997;Guo et al 2001;Kasahara et al 2001;Linder et al 2002Linder et al , 2004Shenoy et al 2005;Sunahara et al 1998;Weber et al 2004), although Cya1, an AC from Rhizobium meliloti has detectable GC activity (Beuve et al 1993). In comparison, various GCs have been shown to have significant AC activity also (Beuve 1999;Linder et al 1999Linder et al , 2000Sunahara et al 1998;Tucker et al 1998).…”

Section: Base Recognition By Chd Active Sitesmentioning

confidence: 99%

Structures, mechanism, regulation and evolution of class III nucleotidyl cyclases

Sinha¹,

Sprang²

2006

Reviews of Physiology Biochemistry and Pharmacology

103

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Cyclic 3 ,5 -guanylyl and adenylyl nucleotides function as second messengers in eukaryotic signal transduction pathways and as sensory transducers in prokaryotes. The nucleotidyl cyclases (NCs) that catalyze the synthesis of these molecules comprise several evolutionarily distinct groups, of which class III is the largest. The domain structures of prokaryotic and eukaryotic class III NCs are diverse, including a variety of regulatory and transmembrane modules. Yet all members of this family contain one or two catalytic domains, characterized by an evolutionarily ancient topological motif (βααββαβ) that is preserved in several other enzymes that catalyze the nucleophilic attack of a 3 -hydroxyl upon a 5 nucleotide phosphate. Two dyad-related catalytic domains compose one catalytic unit, with the catalytic sites formed at the domain interface. The catalytic domains of mononucleotidyl cyclases (MNCs) and diguanylate cyclases (DGCs) are called cyclase homology domains (CHDs) and GGDEF domains, respectively. Prokaryotic NCs usually contain only one catalytic domain and are catalytically active as intermolecular homodimers. The different modes of dimerization in class III NCs probably evolved concurrently with their mode of binding substrate. The catalytic mechanism of GGDEF domain homodimers is not completely understood, but they are expected to have a single active site with each subunit contributing equivalent determinants to bind one GTP molecule or half a c-diGMP molecule. CHD dimers have two potential dyad-related active sites, with both CHDs contributing determinants to each site. Homodimeric class III MNCs have two equivalent catalytic sites, although such enzymes may show half-of-sites reactivity. Eukaryotic class III MNCs often contain two divergent CHDs, with only one catalytically competent site. All CHDs appear to use a common catalytic mechanism, which requires the participation of two magnesium Pharmacol (2006) or manganese ions for binding polyphosphate groups and nucleophile activation. In contrast, mechanisms for purine recognition and specificity are more diverse. Class III NCs are subject to regulation by small molecule effectors, endogenous domains, or exogenous protein partners. Many of these regulators act by altering the interface of the catalytic domains and therefore the integrity of the catalytic site(s). This review focuses on both conserved and divergent mechanisms of class III NC function and regulation.

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“…These GPCR signaling pathways provide a feedback link to modulate activity of ion channels through the activity of cyclic AMP, and thus the behaviors described above that these channels regulate. For example, genes for adenylyl cyclase were cloned from P. tetraurelia and found to localize to cilia, where they potentially regulate K + channels that regulate ciliary movements (Weber et al, 2004). One potential consequence of such a pathway may be the ingestion-mediated hyperpolarization observed in Favella sp., which to our knowledge has not been described in the literature.…”

Section: +mentioning

confidence: 99%

Feast or flee: bioelectrical regulation of feeding and predator evasion behaviors in the planktonic alveolateFavellasp. (Spirotrichia)

Echevarria

Wolfe

Taylor

2015

Journal of Experimental Biology

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Alveolate (ciliates and dinoflagellates) grazers are integral components of the marine food web and must therefore be able to sense a range of mechanical and chemical signals produced by prey and predators, integrating them via signal transduction mechanisms to respond with effective prey capture and predator evasion behaviors. However, the sensory biology of alveolate grazers is poorly understood. Using novel techniques that combine electrophysiological measurements and high-speed videomicroscopy, we investigated the sensory biology of Favella sp., a model alveolate grazer, in the context of its trophic ecology. Favella sp. produced frequent rhythmic depolarizations (∼500 ms long) that caused backward swimming and are responsible for endogenous swimming patterns relevant to foraging. Contact of both prey cells and non-prey polystyrene microspheres at the cilia produced immediate mechanostimulated depolarizations (∼500 ms long) that caused backward swimming, and likely underlie aggregative swimming patterns of Favella sp. in response to patches of prey. Contact of particles at the peristomal cavity that were not suitable for ingestion resulted in depolarizations after a lag of ∼600 ms, allowing time for particles to be processed before rejection. Ingestion of preferred prey particles was accompanied by transient hyperpolarizations (∼1 s) that likely regulate this step of the feeding process. Predation attempts by the copepod Acartia tonsa elicited fast (∼20 ms) animal-like action potentials accompanied by rapid contraction of the cell to avoid predation. We have shown that the sensory mechanisms of Favella sp. are finely tuned to the type, location, and intensity of stimuli from prey and predators.

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Adenylyl cyclases from Plasmodium, Paramecium and Tetrahymena are novel ion channel/enzyme fusion proteins

Cited by 76 publications

References 37 publications

Molecular Details of cAMP Generation in Mammalian Cells: A Tale of Two Systems

Molecular Details of cAMP Generation in Mammalian Cells: A Tale of Two Systems

Structures, mechanism, regulation and evolution of class III nucleotidyl cyclases

Feast or flee: bioelectrical regulation of feeding and predator evasion behaviors in the planktonic alveolateFavellasp. (Spirotrichia)

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