Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion

Hofmann, Franz; Feil, Robert; Kleppisch, Thomas; Schlossmann, Jens

doi:10.1152/physrev.00015.2005

Cited by 358 publications

(347 citation statements)

References 311 publications

(344 reference statements)

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“…It had typical PKG domains (Hofmann et al, 2006) including a serine/threonine kinase domain (with a catalytic site) and two cGMPbinding domains. The same degenerate primers and techniques were used to clone the L. migratoria for ortholog lmfor (GenBank accession number FJ214984).…”

Section: The Locust Foraging Gene the Locust Foraging Genementioning

confidence: 99%

The locust foraging gene

Lucas

Kornfein

Chakaborty-Chatterjee

et al. 2010

Arch Insect Biochem Physiol

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Our knowledge of how genes act on the nervous system in response to the environment to generate behavioral plasticity is limited. A number of recent advancements in this area concern food-related behaviors and a specific gene family called foraging (for), which encodes a cGMPdependent protein kinase (PKG). The desert locust (Schistocerca gregaria) is notorious for its destructive feeding and long-term migratory behavior. Locust phase polyphenism is an extreme example of environmentally induced behavioral plasticity. In response to changes in population density, locusts dramatically alter their behavior, from solitary and relatively sedentary behavior to active aggregation and swarming. Very little is known about the molecular and genetic basis of this striking behavioral phenomenon. Here we initiated studies into the locust for gene by identifying, cloning, and studying expression of the gene in the locust brain. We determined the phylogenetic relationships between the locust PKG and other known PKG proteins in insects. FOR expression was found to be confined to neurons of the anterior midline of the brain, the pars intercerebralis. Our results suggest that differences in PKG enzyme activity are correlated to well-established phase-related behavioral differences. These results lay the groundwork for functional studies of the locust for gene and its possible relations to locust phase polyphenism.

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Section: The Locust Foraging Gene the Locust Foraging Genementioning

confidence: 99%

The locust foraging gene

Lucas

Kornfein

Chakaborty-Chatterjee

et al. 2010

Arch Insect Biochem Physiol

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“…2, B and C). In this study, a PKG-I knockout mouse was not used due to its very limited lifespan (ϳ4 wk) (20).…”

Section: Renal Ir Injury Downregulates Kidney Pkg-i Levelsmentioning

confidence: 99%

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Tong

Maimaitiyiming

et al. 2012

American Journal of Physiology-Renal Physiology

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Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury. Am J Physiol Renal Physiol 302: F561-F570, 2012. First published December 7, 2011 doi:10.1152/ajprenal.00355.2011.-cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/ activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG

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“…In mammals, PKG is important for proper induction of long-term potentiation (LTP) and long-term depression (LTD) (Hartell 1994;Zhuo et al 1994;Lev-Ram et al 1997;Arancio et al 2001;Fiel et al 2003Fiel et al , 2005Kleppisch et al 2003;Hofmann et al 2006). Although LTP and LTD are thought to be important mechanisms underlying learning and memory (Whitlock et al 2006), few studies have shown a direct role for PKG in learning and memory.…”

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confidence: 99%

Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase

Kaun

Hendel²,

Gerber³

et al. 2007

Learn. Mem.

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Animals must be able to find and evaluate food to ensure survival. The ability to associate a cue with the presence of food is advantageous because it allows an animal to quickly identify a situation associated with a good, bad, or even harmful food. Identifying genes underlying these natural learned responses is essential to understanding this ability. Here, we investigate whether natural variation in the foraging (for) gene in Drosophila melanogaster larvae is important in mediating associations between either an odor or a light stimulus and food reward. We found that for influences olfactory conditioning and that the mushroom bodies play a role in this for-mediated olfactory learning. Genotypes associated with high activity of the product of for, cGMP-dependent protein kinase (PKG), showed greater memory acquisition and retention compared with genotypes associated with low activity of PKG when trained with three conditioning trials. Interestingly, increasing the number of training trials resulted in decreased memory retention only in genotypes associated with high PKG activity. The difference in the dynamics of memory acquisition and retention between variants of for suggests that the ability to learn and retain an association may be linked to the foraging strategies of the two variants.Learned associations such as identifying odors as indicators of food, or showing preferences for food-related odors, are conserved across diverse taxa from humans and mice to slugs, honeybees, and fruit flies (Ache and Young 2005). The fruit fly Drosophila melanogaster can use odors as cues for the presence of both a food reward and an aversive stimulus (Tempel et al. 1983;Scherer et al. 2003;Schwaerzel et al. 2003;Margulies et al. 2005;McGuire et al. 2005;Kim et al. 2007). Identifying genes underlying these natural learned responses is essential to understanding this ability. Here, we use classical reward conditioning to investigate how natural variation in the foraging (for) gene affects acquisition and decay of memory in D. melanogaster larvae.for encodes a cGMP-dependent protein kinase (PKG) (Osborne et al. 1997). In mammals, PKG is important for proper induction of long-term potentiation (LTP) and long-term depression (LTD) (Hartell 1994;Zhuo et al. 1994;Lev-Ram et al. 1997;Arancio et al. 2001;Fiel et al. 2003Fiel et al. , 2005Kleppisch et al. 2003;Hofmann et al. 2006). Although LTP and LTD are thought to be important mechanisms underlying learning and memory (Whitlock et al. 2006), few studies have shown a direct role for PKG in learning and memory. This study aims to do this by investigating how learning differs between allelic variants of for in Drosophila larvae.for is an ideal candidate to study how natural genetic variation can affect learning and memory, since natural for variants exist that have subtle but significant variations in PKG activity (Osborne et al. 1997). The rover variants of for (for R ) have higher for transcript levels and higher PKG activities compared with the sitter variants of for (for s ) (Osb...

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Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion

Cited by 358 publications

References 311 publications

The locust foraging gene

The locust foraging gene

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase

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