Dynamic re‐distribution of protein kinase D (PKD) as revealed by a GFP‐PKD fusion protein: dissociation from PKD activation

Matthews, Sharon A.; Iglesias, Teresa; Cantrell, Doreen A.

doi:10.1016/s0014-5793(99)01090-x

Cited by 68 publications

(98 citation statements)

References 32 publications

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“…Phorbol ester treatment is known to cause plasma membrane translocation and activation of PKD (Zugaza et al, 1996;Matthews et al, 1999;Rey et al, 2004). In live cell imaging of hippocampal neurons, 1 M PDBu treatment led to a rapid recruitment of wtPKD1-EGFP to the plasma membrane, followed by the intracellular accumulation of the fluorescently tagged protein ( Figure 1B).…”

Section: Pkd Is Localized At the Trans-golgi Network In Neuronsmentioning

confidence: 98%

“…Besides a rather homogenous cytoplasmic distribution, wtPKD1-EGFP was significantly enriched at the Golgi apparatus (Table 1). On closer examination, wtPKD1-EGFP was localized side by side with GM130 but showed partially overlapping localization with VAMP4-stained structures ( Figure 1A, enlargements).Phorbol ester treatment is known to cause plasma membrane translocation and activation of PKD (Zugaza et al, 1996;Matthews et al, 1999;Rey et al, 2004). In live cell imaging of hippocampal neurons, 1 M PDBu treatment led to a rapid recruitment of wtPKD1-EGFP to the plasma membrane, followed by the intracellular accumulation of the fluorescently tagged protein ( Figure 1B).…”

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confidence: 97%

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Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

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Protein kinase D (PKD) is known to participate in various cellular functions, including secretory vesicle fission from theGolgi and plasma membrane-directed transport. Here, we report on expression and function of PKD in hippocampal neurons. Expression of an enhanced green fluorescent protein (EGFP)-tagged PKD activity reporter in mouse embryonal hippocampal neurons revealed high endogenous PKD activity at the Golgi complex and in the dendrites, whereas PKD activity was excluded from the axon in parallel with axonal maturation. Expression of fluorescently tagged wild-type PKD1 and constitutively active PKD1 S738/742E (caPKD1) in neurons revealed that both proteins were slightly enriched at the trans-Golgi network (TGN) and did not interfere with its thread-like morphology. By contrast, expression of dominant-negative kinase inactive PKD1 K612W (kdPKD1) led to the disruption of the neuronal Golgi complex, with kdPKD1 strongly localized to the TGN fragments. Similar findings were obtained from transgenic mice with inducible, neuron-specific expression of kdPKD1-EGFP. As a prominent consequence of kdPKD1 expression, the dendritic tree of transfected neurons was reduced, whereas caPKD1 increased dendritic arborization. Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons. INTRODUCTIONNeurons are nondividing and extremely polarized cells, with enormous membrane surface compared with the size of the soma. These features assume a highly specialized secretory machinery, which resembles in certain parts the directed transport mechanisms described in polarized nonneuronal cells (Winckler and Mellman, 1999;Horton and Ehlers, 2004). The vast neuronal membrane surface is functionally and structurally divided into axonal and somatodendritic compartments, possessing specific lipid and protein components required for the spatially different functions, e.g., for pre-or postsynaptic activity (Dresbach et al., 2001;Sheng, 2001;Bresler et al., 2004). The constitutive and precisely directed supply of surface membrane components is indispensable for the function of neurons, especially when considering that postmitotic neurons normally serve throughout the life span of the organism. Up to now, we are far from understanding how the extreme polarization has been evolved and is maintained in neurons.Despite a likely central role in neuronal morphogenesis and membrane trafficking, little is known about the special structure and transport features of the neuronal Golgi apparatus. A thread-like and reticular structure of the Golgi apparatus has been already described in many neuronal types (Takamine et al., 2000;Fujita and Okamoto, 2005;Horton et al., 2005). Central neuronal Golgi complex is localized in the soma and often extends into the principal dendrites, but Golgi elements were also found as discontinuous structures in the distal dendrites, often near synaptic contacts or in dendritic spines (Gardiol et al., 1999;Pierc...

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Section: Pkd Is Localized At the Trans-golgi Network In Neuronsmentioning

confidence: 98%

mentioning

confidence: 97%

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Czöndör

Ellwanger²,

Fuchs³

et al. 2009

MBoC

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“…At 48 h after transfection, cells were incubated in low-serum medium (0.5% FBS) for 16 -18 h and then treated with senktide (1 M) or vehicle for various times before immunostaining or Western blotting. The human PKD1, -2, and -3-GFP transcripts have been described (25,36,37), as has the rat NK 3R with NH2-terminal FLAG epitope (43). Human PKCε-EGFP transcript was a gift from Dr. Daria Mochly-Rosen (Stanford University) (41).…”

Section: Methodsmentioning

confidence: 99%

“…DAG analogs promote membrane translocation of PKD in IPANs. Since PKD translocates in response to DAG and DAG analogs (25), we examined the effects of DAG analogs on the subcellular distribution of PKD1/2 in myenteric IPANs. Exposure to phorbol or ingenol esters resulted in the translocation of PKD1/2 from the cytoplasm to the plasma membrane of NeuNcyt-IR neurons (Fig.…”

Section: Pkd Is Localized To Ipans Of the Myenteric Plexusmentioning

confidence: 99%

Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons

Poole¹,

Amadesi²,

Thacker³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Poole DP, Amadesi S, Rozengurt E, Thacker M, Bunnett NW, Furness JB. Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons. Am J Physiol Gastrointest Liver Physiol 294: G1245-G1256, 2008. First published February 28, 2008 doi:10.1152/ajpgi.00521.2007.-Tachykinins, acting through NK 3 receptors (NK3R), contribute to excitatory transmission to intrinsic primary afferent neurons (IPANs) of the small intestine. Although this transmission is dependent on protein kinase C (PKC), its maintenance could depend on protein kinase D (PKD), a downstream target of PKC. Here we show that PKD1/2-immunoreactivity occurred exclusively in IPANs of the guinea pig ileum, demonstrated by double staining with the IPAN marker NeuN. PKCε was also colocalized with PKD1/2 in IPANs. PKCε and PKD1/2 trafficking was studied in enteric neurons within whole mounts of the ileal wall. In untreated preparations, PKCε and PKD1/2 were cytosolic and no signal for activated (phosphorylated) PKD was detected. The NK 3R agonist senktide evoked a transient translocation of PKCε and PKD1/2 from the cytosol to the plasma membrane and induced PKD1/2 phosphorylation at the plasma membrane. PKCε translocation was maximal at 10 s and returned to the cytosol within 2 min. Phosphorylated-PKD1/2 was detected at the plasma membrane within 15 s and translocated to the cytosol by 2 min, where it remained active up to 30 min after NK3R stimulation. PKD1/2 activation was reduced by a PKCε inhibitor and prevented by NK3R inhibition. NK3R-mediated PKCε and PKD activation was confirmed in HEK293 cells transiently expressing NK3R and green fluorescent protein-tagged PKCε, PKD1, PKD2, or PKD3. Senktide caused membrane translocation and activation of kinases within 30 s. After 15 min, phosphorylated PKD had returned to the cytosol. PKD activation was confirmed through Western blotting. Thus stimulation of NK3R activates PKCε and PKD in sequence, and sequential activation of these kinases may account for rapid and prolonged modulation of IPAN function.tachykinins; primary afferent neurons THE THREE MAJOR TACHYKININ (neurokinin) receptors, NK 1 R, NK 2 R, and NK 3 R, are differentially expressed throughout the gastrointestinal tract. The principal endogenous tachykinins of enteric neurons are substance P and neurokinin A, neurokinin B being absent from enteric neurons (14). A major functional role of the NK 3 R in the gastrointestinal tract is to mediate noncholinergic slow excitatory postsynaptic potentials (sEPSPs) in myenteric intrinsic primary afferent neurons (IPANs) of the guinea pig ileum, thereby augmenting the excitability of these neurons (4). Similar transmission occurs in other regions of the gut, including the stomach, duodenum, and gallbladder (29, 42), suggesting a general functional role of NK 3 R in the enteric nervous system. Although NK 3 R has been shown to be involved in generating sEPSPs, NK 3 R antagonists fail to alter peristaltic contractions of the guinea pig small intestine (16). It has been s...

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“…As no interactions have been found between the PH domain of PKD1 and phosphorylated inositol lipids, which are important ligands responsible for membrane localization, this domain is not required for plasma membrane translocation [31,32] or Golgi localization [33][34][35][36][37][38][39] like other PH-domain-containing AGC kinases, such as PKB and the GRKs. However, the PH domain is required for the nuclear export of PKD1 [22,40] .…”

Section: The Pkd Family Belongs To the Camk Groupmentioning

confidence: 99%

Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system

Wang

2014

Neurosci. Bull.

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Protein kinase D (PKD) is an evolutionarily-conserved family of protein kinases. It has structural, regulatory, and enzymatic properties quite different from the PKC family. Many stimuli induce PKD signaling, including G-protein-coupled receptor agonists and growth factors. PKD1 is the most studied member of the family. It functions during cell proliferation, differentiation, secretion, cardiac hypertrophy, immune regulation, angiogenesis, and cancer. Previously, we found that PKD1 is also critically involved in pain modulation. Since then, a series of studies performed in our lab and by other groups have shown that PKDs also participate in other processes in the nervous system including neuronal polarity establishment, neuroprotection, and learning. Here, we discuss the connections between PKD structure, enzyme function, and localization, and summarize the recent fi ndings on the roles of PKD-mediated signaling in the nervous system. Keywords: PKD; neuronal polarity; pain modulation; neuroprotection; learning IntroductionMembers of the protein kinase D (PKD) family are diacylglycerol (DAG) and protein kinase C (PKC) effectors.They are activated by the actions of hormones, growth factors, neurotransmitters, and other stimuli through phospholipase C (PLC) [1] . Three widely-expressed mammalian homologs are PKD1 (mouse PKD, human PKCμ) [2,3] , PKD2 [3] , and PKD3 [4] (also named PKC), but the levels of individual PKDs vary in different tissues.Recent fi ndings have revealed that PKDs participate in the regulation of Golgi function through modulating the fi ssion of vesicles from the trans-Golgi network (TGN) [5,6] . Other recent reports have shown that PKDs function during cell proliferation and apoptosis, carcinogenesis, and intracellular trafficking. Here, we describe the connections between PKD structure, enzymatic function, and localization, and then summarize recent fi ndings on the roles of PKD in the nervous system. The PKD Family Belongs to the CaMK GroupThe PKD family comprises PKD1, PKD2, and PKD3. PKD was initially described as an atypical isoform of the PKC family [7] , which is a member of the protein kinase A, G, and C (AGC) serine/threonine kinase subfamily [8,9] . However, later studies revealed that PKD has mixed features of different subclasses of the PKC family, so it does not belong to any one of them. For example, its pleckstrin-homology (PH) domain is closely related to the PKB and G-proteincoupled receptor kinase (GRK) families and is not found in any PKC enzyme, while the cysteine-rich domains are more reminiscent of classical and novel PKCs. The structure and function of the catalytic domain of PKD are quite different from those of the AGC/PKC family members [2][3][4]10] . Indeed, PKD has now been classified as a new family within the (Fig. 1). The elaborate constitution of PKD1 is intricately linked to its catalytic functions, regulation, and intracellular localization (Table 1). PKD1 can be activated through different pathways.First, some stimuli activate PLC, which induces PKD phosp...

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Dynamic re‐distribution of protein kinase D (PKD) as revealed by a GFP‐PKD fusion protein: dissociation from PKD activation

Cited by 68 publications

References 32 publications

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Stimulation of the neurokinin 3 receptor activates protein kinase Cε and protein kinase D in enteric neurons

Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system

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