Structure, bioactivity, and cellular localization of myomodulin B: A novel Aplysia peptide

Cropper, Elizabeth; Vilim, Ferdinand S.; Alevizos, A.; Tenenbaum, Renata; Kolks, Mary Ann Gawinowicz; Rosen, Steven C.; Kupfermann, Irving; Weiss, Klaudiusz R.

doi:10.1016/0196-9781(91)90120-e

Cited by 51 publications

(54 citation statements)

References 9 publications

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“…1, right; for review and complete references see Brezina et al 2003aBrezina et al , 2005Hooper et al 1999;Kupfermann et al 1997;Weiss et al 1993). Most important are the small cardioactive peptides (SCPs), released from motor neuron B15 (e.g., Cropper et al 1987a;Lloyd et al 1984;Vilim et al 1996b), and the myomodulins (MMs), released from motor neuron B16 Cropper et al 1987bCropper et al , 1991Vilim et al 2000). The SCPs and MMs shape contractions through three main effects on the muscle: 1) they potentiate the contractions by enhancing the muscle's depolarization-activated Ca current that supplies Ca 2ϩ essential for contraction (e.g., Brezina et al 1994a; 2) they depress the contractions by activating in the muscle a K current that opposes the ACh-induced depolarization, activation of the Ca current, and Ca 2ϩ influx (Brezina et al 1994bOrekhova et al 2003); and 3) they increase the relaxation rate of the contractions probably by modulating the muscle's contractile machinery (Heierhorst et al , 1995Probst et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Temperature Compensation of Neuromuscular Modulation inAplysia

Zhurov¹,

Březina²

2005

Journal of Neurophysiology

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. Physiological systems that must operate over a range of temperatures often incorporate temperature-compensatory mechanisms to maintain their output within a relatively narrow, functional range of values. We analyze here an example in the accessory radula closer (ARC) neuromuscular system, a representative part of the feeding neuromusculature of the sea slug Aplysia. The ARC muscle's two motor neurons, B15 and B16, release, in addition to ACh that contracts the muscle, modulatory peptide cotransmitters that, through a complex network of effects in the muscle, shape the ACh-induced contractions. It is believed that this modulation is critical in optimizing the performance of the muscle for successful, efficient feeding behavior. However, previous work has shown that the release of the modulatory peptides from the motor neurons decreases dramatically with increasing temperature. From 15 to 25°C, for example, release decreases 20-fold. Yet Aplysia live and feed successfully not only at 15°C, but at 25°C and probably at higher temperatures. Here, working with reduced B15/B16 -ARC preparations in vitro as well as a mathematical model of the system, we have found a resolution of this apparent paradox. Although modulator release decreases 20-fold when the temperature is raised from 15 to 25°C, the observed modulation of contraction shape does not decrease at all. Two mechanisms are responsible. First, further downstream within the modulatory network, the modulatory effects themselves-experimentally dissected by exogenous modulator application-have temperature dependencies opposite to that of modulator release, increasing with temperature. Second, the saturating curvature of the dose-response relations within the network diminishes the downstream impact of the decrease of modulator release. Thus two quite distinct mechanisms, one depending on the characteristics of the individual components of the network and the other emerging from the network's structure, combine to compensate for temperature changes to maintain the output of this physiological system. I N T R O D U C T I O NThe rates of individual biochemical reactions and elementary physiological processes vary intrinsically with temperature. Yet the larger physiological systems that are built from these processes must often maintain their output within a relatively narrow, functional range of values. Animals that are active over a range of environmental temperatures must therefore compensate, if they do not regulate their internal temperature, by building temperature-compensatory mechanisms into the structure of their physiological systems. We analyze here an example in the accessory radula closer (ARC) neuromuscular system of the sea slug Aplysia. This system is tuned by a complex network of neuromodulatory effects that, individually, vary greatly with temperature; yet the overall output of the system does not.The ARC muscle is one of the muscles of the buccal mass, a complex structure that produces rhythmic, cyclical movements of the animal's food-grasping organ...

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Section: Introductionmentioning

confidence: 99%

Temperature Compensation of Neuromuscular Modulation inAplysia

Zhurov¹,

Březina²

2005

Journal of Neurophysiology

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“…B15 releases, in particular, the small cardioactive peptides (SCPs) (Cropper et al 1987a(Cropper et al , 1990aLloyd et al 1984;Vilim et al 1996a;Whim and Lloyd 1989), and B16 releases the myomodulins (MMs) Cropper et al 1987bCropper et al , 1991Vilim et al 2000). The SCPs and MMs shape contractions through 3 main actions on the muscle: 1) they potentiate the contractions by enhancing the muscle's depolarization-activated Ca current that supplies Ca 2ϩ essential for contraction Brezina et al 1994aCropper et al 1987aCropper et al ,b, 1991Lloyd et al 1984;Whim and Lloyd 1990;); 2) they depress the contractions by activating in the muscle a K current that opposes the ACh-induced depolarization, activation of the Ca current, and Ca 2ϩ influx (Brezina et al 1994bCropper et al 1987bCropper et al , 1991; and 3) they increase the relaxation rate of the contractions probably by modulating the muscle's contractile machinery Cropper et al 1990a;Heierhorst et al 1995;Probst et al 1994;Whim and Lloyd 1990). The balance of the competing potentiating and depressing actions determines the net modulation of contraction size, which, together with the modulation of the relaxation rate, then gives the final shape of the contraction (see Brezina et al 2000a).…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular Modulation inAplysia. I. Dynamic Model

Březina

Orekhova

Weiss

2003

Journal of Neurophysiology

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. Many physiological systems are regulated by complex networks of modulatory actions. Here we use mathematical modeling and complementary experiments to study the dynamic behavior of such a network in the accessory radula closer (ARC) neuromuscular system of Aplysia. The ARC muscle participates in several types of rhythmic consummatory feeding behavior. The muscle's motor neurons release acetylcholine to produce basal contractions, but also modulatory peptide cotransmitters that, through multiple cellular effects, shape the contractions to meet behavioral demands. We construct a dynamic model of the modulatory network and examine its operation as the motor neurons fire in realistic patterns that change gradually over an hour-long meal and abruptly with switches between the different feeding behaviors. The modulatory effects have very disparate dynamical time scales. Some react to the motor neuron firing only over many cycles of the behavior, but one key effect is fast enough to respond to each individual cycle. Switches between the behaviors are therefore followed by rapid relaxations along some modulatory dimensions but not others. The trajectory of the modulatory state is a transient throughout the meal, ranging widely over regions of the modulatory space not accessible in the steady state. There is a pronounced history-dependency: the modulatory state associated with a cycle of a particular behavior depends on when that cycle occurs and what behaviors preceded it. On average, nevertheless, each behavior is associated with a different modulatory state. In the following companion study, we add a model of the neuromuscular transform to reconstruct and evaluate the actual modulated contraction shapes.

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“…An important example of this structural diversity is the myomodulin family of molluscan neuropeptides. Myomodulin A (PMSMLRLamide) and eight related peptides were first discovered by molecular and biochemical methods in Aplysia (Cropper et al, 1987(Cropper et al, , 1991Lopez et al, 1993;Miller et al, 1993;Brezina et al, 1995). Myomodulin A is now known to be present in several other molluscs together with at least one more related molecule (Fugisawa et al, 1990), and further types of myomodulin are also likely to be discovered with further investigation.…”

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confidence: 99%

“…Studies aimed at understanding the signaling function of neuropeptides have emphasized the value of using model invertebrate systems, such as gastropod molluscs, in which the pattern of gene expression and the physiological function of processed peptides can be studied at the level of single identified neurons (Cropper et al, 1987(Cropper et al, , 1991Benjamin and Burke, 1994). A common feature of invertebrate neuropeptide genes is that they encode a variety of structurally related peptides present on one or more precursor proteins.…”

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Myomodulin Gene ofLymnaea: Structure, Expression, and Analysis of Neuropeptides

et al. 1996

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The myomodulin family of neuropeptides is an important group of neural cotransmitters in molluscs and is known to be present in the neural network that controls feeding behavior in the snailLymnaea. Here we show that a single gene encodes five structurally similar forms of myomodulin: GLQMLRLamide, QIPMLRLamide, SMSMLRLamide, SLSMLRLamide, and PMSMLRLamide, the latter being present in nine copies. Analysis of the organization of the gene indicates that it is transcribed as a single spliced transcript from an upstream promoter region that contains multiple cAMP-responsive elements, as well as putative elements with homology to tissue-specific promoter-binding sites. The presence in nervous tissue of two of the peptides, GLQMLRLamide and PMSMLRLamide, is confirmed by mass spectrometry.In situhybridization analysis indicates that the gene is expressed in specific cells in all ganglia of the CNS ofLymnaea, which will allow physiological analysis of the function of myomodulins at the level of single identified neurons.

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Structure, bioactivity, and cellular localization of myomodulin B: A novel Aplysia peptide

Cited by 51 publications

References 9 publications

Temperature Compensation of Neuromuscular Modulation inAplysia

Temperature Compensation of Neuromuscular Modulation inAplysia

Neuromuscular Modulation inAplysia. I. Dynamic Model

Myomodulin Gene ofLymnaea: Structure, Expression, and Analysis of Neuropeptides

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