Serotonin induces selective cleavage of the PKA RI subunit but not RII subunit in Aplysia neurons

Kurosu, Takeshi; Hernández, A. Iván; Schwartz, James H.

doi:10.1016/j.bbrc.2007.05.146

Cited by 8 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the absence of cAMP, C and R subunits assemble into inactive R 2 C 2 complexes; active C subunits are released upon binding of cAMP to R. In this equilibrium reaction, a decreased R:C ratio leads to the release of more catalytic activity for a given concentration of cAMP (46), as recently demonstrated by RNAi against PKAR1A in HEK293 cells (45). In Aplysia neurons, 5-HT induces cleavage of the R1 subunit but not the R2 subunit (47). A reduction in PKAR1 would thus potentiate the effect of any 5-HT released in response to gregarizing sensory stimuli, resulting in the increased gregariousness we observed.…”

Section: Discussionmentioning

confidence: 85%

Critical role for protein kinase A in the acquisition of gregarious behavior in the desert locust

Ott

Verlinden

Rogers

et al. 2011

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

View full text Add to dashboard Cite

The mechanisms that integrate genetic and environmental information to coordinate the expression of complex phenotypes are little understood. We investigated the role of two protein kinases (PKs) in the population density-dependent transition to gregarious behavior that underlies swarm formation in desert locusts: the foraging gene product, a cGMP-dependent PK (PKG) implicated in switching between alternative group-related behaviors in several animal species; and cAMP-dependent PK (PKA), a signal transduction protein with a preeminent role in different forms of learning. Solitarious locusts acquire key behavioral characters of the swarming gregarious phase within just 1 to 4 h of forced crowding. Injecting the PKA inhibitor KT5720 before crowding prevented this transition, whereas injecting KT5823, an inhibitor of PKG, did not. Neither drug altered the behavior of long-term gregarious locusts. RNAi against foraging effectively reduced its expression in the central nervous system, but this did not prevent gregarization upon crowding. By contrast, solitarious locusts with an RNAi-induced reduction in PKA catalytic subunit C1 expression behaved less gregariously after crowding, and RNAi against the inhibitory R1 subunit promoted more extensive gregarization following a brief crowding period. A central role of PKA is congruent with the recent discovery that serotonin mediates gregarization in locusts and with findings in vertebrates that similarly implicate PKA in the capacity to cope with adverse life events. Our results show that PKA has been coopted into effecting the wide-ranging transformation from solitarious to gregarious behavior, with PKAmediated behavioral plasticity resulting in an environmentally driven reorganization of a complex phenotype.phase change | phenotypic plasticity | Schistocerca gregaria H ow genetic information is integrated with environmental cues to control and coordinate complex phenotypes is a fundamental question in biology (1, 2). Environmental input can cause concerted changes in multiple traits to produce distinct phenotypic syndromes that are adaptive in particular conditions. Phase polyphenism in desert locusts (Schistocerca gregaria) is an extreme example. Locusts can reversibly transform between a solitarious phase and a gregarious phase that differ profoundly in morphology, physiology, and behavior (3-5). Solitarious locusts occur at low population densities and actively avoid conspecifics; they are cryptic in appearance and behavior; walk with a slow, creeping gait; and have restricted dietary preferences. The gregarious phase is characterized by increased activity and locomotion, an upright posture and gait, aposematic coloration, a broad dietary range, and, most critically, attraction to other locusts. Phase change is driven by huge changes in population density and is an adaptation to arid habitats where rains are infrequent and erratic. Transitory periods of verdure support rapid population growth, but after the rains cease, large numbers of solitarious locusts compete for...

show abstract

Section: Discussionmentioning

confidence: 85%

Critical role for protein kinase A in the acquisition of gregarious behavior in the desert locust

Ott

Verlinden

Rogers

et al. 2011

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

View full text Add to dashboard Cite

show abstract

“…RI is mostly soluble in the soma, whereas RII is enriched at nerve terminals (32). Repeated or prolonged 5-HT induces degradation of RI, relieving its inhibition of the catalytic subunit, thus giving rise to increased PKA activity (18,33). Similar mechanisms may underlie the delayed increase in somatic PKA activity after repeated TNS.…”

Section: Spatiotemporal Regulation Of Mapk and Pka Signaling In Memorymentioning

confidence: 91%

“…Similar mechanisms may underlie the delayed increase in somatic PKA activity after repeated TNS. In contrast, 5-HT does not lead to RII degradation (33), suggesting that a different mechanism may be engaged to prolong synaptic PKA activation. One critical regulator of the duration of synaptic PKA activation is phosphodiesterase-4 (PDE4), which can be phosphorylated by MAPK, in turn reducing its activity (34).…”

Section: Spatiotemporal Regulation Of Mapk and Pka Signaling In Memorymentioning

confidence: 92%

Local synaptic integration of mitogen-activated protein kinase and protein kinase A signaling mediates intermediate-term synaptic facilitation in Aplysia

Ye¹,

Marina²,

Carew³

2012

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

View full text Add to dashboard Cite

It is widely appreciated that memory processing engages a wide range of molecular signaling cascades in neurons, but how these cascades are temporally and spatially integrated is not well understood. To explore this important question, we used Aplysia californica as a model system. We simultaneously examined the timing and subcellular location of two signaling molecules, MAPK (ERK1/2) and protein kinase A (PKA), both of which are critical for the formation of enduring memory for sensitization. We also explored their interaction during the formation of enduring synaptic facilitation, a cellular correlate of memory, at tail sensory-to-motor neuron synapses. We find that repeated tail nerve shock (TNS, an analog of sensitizing training) immediately and persistently activates MAPK in both sensory neuron somata and synaptic neuropil. In contrast, we observe immediate PKA activation only in the synaptic neuropil. It is followed by PKA activation in both compartments 1 h after TNS. Interestingly, blocking MAPK activation during, but not after, TNS impairs PKA activation in synaptic neuropil without affecting the delayed PKA activation in sensory neuron somata. Finally, by applying inhibitors restricted to the synaptic compartment, we show that synaptic MAPK activation during TNS is required for the induction of intermediate-term synaptic facilitation, which leads to the persistent synaptic PKA activation required to maintain this facilitation. Collectively, our results elucidate how MAPK and PKA signaling cascades are spatiotemporally integrated in a single neuron to support synaptic plasticity underlying memory formation. D uring signal transduction, single molecules often generate different cellular effects, depending on their temporal dynamics, spatial distribution, and interacting partners (1). In considering the wide range of molecules implicated in memory processing, the question of how multiple signaling cascades are integrated in time and space to contribute to memory formation and its underlying synaptic plasticity remains a fundamental issue.We have begun to explore this general question in Aplysia californica, a model system well suited for mechanistic analyses of simple forms of learning. We focused on two molecules, MAPK (ERK1/2) and protein kinase A (PKA), both known to be engaged in many forms of memory and synaptic plasticity (2-4). Recent studies, however, suggest the timing, cellular location, and crosstalk between these kinases are critical in determining their ultimate effects (5-10). Thus, in addition to knowing that MAPK and PKA are required, it also is important to understand their spatiotemporal dynamics and their interactions during memory formation.Aplysia provides unique advantages for analyzing these questions. In Aplysia, memory for sensitization induced by tail shock (TS) is supported in large measure by synaptic facilitation at identified tail sensory-to-motor neuron (SN-MN) synapses (11). As an analog of behavioral training, tail nerve shock (TNS) also induces synaptic facilitation (12)(...

show abstract

“…In contrast, if the application of 5HT is continuous (25 min of continuous 5HT), then these protocols are ineffective at inducing LTF and weaker at inducing ITF (Mauelshagen et al, 1998;Sutton et al, 2002). Although longer continuous applications of 5HT (90 min) do induce both ITF (Yanow et al, 1998) and LTF (Zhang et al, 1997), they do not persistently activate PKA (Müller and Carew, 1998; but see Kurosu et al, 2007), suggesting that this ITF may be mediated by a different molecular trace. Indeed, massed applications of 5HT persistently activate the novel PKC Apl II (Sossin, 1997).…”

Section: Introductionmentioning

confidence: 94%

PKC Differentially Translocates during Spaced and Massed Training inAplysia

Farah¹,

Weatherill²,

Dunn³

et al. 2009

J. Neurosci.

View full text Add to dashboard Cite

Learning is highly regulated by the pattern of training. In Aplysia, an important organism for the development of cellular and molecular models of learning, spaced versus massed application of the same stimulus leads to different forms of memory. A critical molecular step underlying memory is the serotonin (5HT)-mediated activation of the novel PKC Apl II. Here, we demonstrate that activation of PKC Apl II is highly sensitive to the pattern of 5HT application. Spaced applications downregulate PKC translocation through PKA signaling, whereas massed applications lead to persistent translocation of PKC. Differential regulation of PKC translocation is mediated by competing feedback mechanisms that act through protein synthesis. These studies elucidate a fundamental molecular difference between spaced and massed training protocols.

show abstract

Serotonin induces selective cleavage of the PKA RI subunit but not RII subunit in Aplysia neurons

Cited by 8 publications

References 29 publications

Critical role for protein kinase A in the acquisition of gregarious behavior in the desert locust

Critical role for protein kinase A in the acquisition of gregarious behavior in the desert locust

Local synaptic integration of mitogen-activated protein kinase and protein kinase A signaling mediates intermediate-term synaptic facilitation in Aplysia

PKC Differentially Translocates during Spaced and Massed Training inAplysia

Contact Info

Product

Resources

About