Prominent Dendritic Localization in Forebrain Neurons of a Novel mRNA and Its Product, Dendrin

Herb, Anne; Wisden, William; Catania, Maria Vincenza; Maréchal, Daniel; Dresse, A; Seeburg, Peter H.

doi:10.1006/mcne.1996.0594

Cited by 65 publications

(41 citation statements)

References 27 publications

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“…Using Western blotting, anti-dendrin antisera recognized a protein that was approximately 80 kD ( Figure 2). This is in line with the published rat dendrin protein size (81 kD) (30).…”

Section: Dendrinsupporting

confidence: 91%

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Expression and Subcellular Distribution of Novel Glomerulus-Associated Proteins Dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik

Patrakka¹,

Xiao²,

Nukui³

et al. 2007

Journal of the American Society of Nephrology

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The glomerular capillary tuft is a highly specialized microcapillary that is dedicated to function as a sophisticated molecular sieve. The glomerulus filter has a unique molecular composition, and several essential glomerular proteins are expressed in the kidney exclusively by glomerular podocytes. A catalog of >300 glomerulus-upregulated transcripts that were identified using expressed sequence tag profiling and microarray analysis was published recently. This study characterized the expression profile of five glomerulus-upregulated transcripts/proteins (ehd3, dendrin, sh2d4a, plekhh2, and 2310066E14Rik) in detail. The expression pattern of these novel glomerular transcripts in various mouse tissues was studied using reverse transcriptase-PCR, Northern blotting, and in situ hybridization. For studying the distribution of corresponding proteins, polyclonal antibodies were raised against the gene products, and Western blotting, immunofluorescence, and immunoelectron microscopic analyses were performed. Remarkably, it was discovered that all five transcripts/proteins were expressed in the kidney exclusively by glomerular cells. Ehd3 was expressed only by glomerular endothelial cells. Importantly, ehd3 is the first gene ever shown to be expressed exclusively by glomerular endothelial cells and not by other endothelial cells in the kidney. Dendrin, sh2d4a, plekhh2, and 2310066E14Rik, however, were transcribed solely by podocytes. With the use of polyclonal antibodies, dendrin, sh2d4a, and plekhh2 proteins were localized to the slit diaphragm and the foot process, whereas 2310066E14Rik protein was localized to the podocyte major processes and cell body. This study provides fresh insights into glomerular biology and uncovers new possibilities to explore the role of these novel proteins in the glomerular physiology and pathology. T he glomerular capillary tuft of the kidney is a unique micro-organ that is specialized to operate as a sophisticated molecular sieve (1). The filtration barrier is composed of the glomerular endothelial cells (GEC), the glomerular basement membrane (GBM), and the podocyte cells. GEC differ from most other endothelial cells in that they are extraordinarily flattened and fenestrated (2). The fenestrated structure of GEC depends on podocyte-derived vascular endothelial growth factor A (3), but the mechanisms behind their unique structure largely are unknown. The GBM, like all basement membranes (BM), is composed of interconnected collagen type IV and laminin networks, where proteoglycans and other matrix components are attached. The GBM, however, is distinct from most other BM of the body, because it contains a unique composition of collagen type IV and laminin isoforms. The importance of these components is highlighted by the fact that defects in GBM-specific type IV collagen or laminin lead to Alport syndrome and Pierson syndrome, respectively (4 -6).The podocyte foot processes and the slit diaphragm serve as a final filtration barrier in the glomerulus. This filtration machinery contains a n...

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“…Using Western blotting, anti-dendrin antisera recognized a protein that was approximately 80 kD ( Figure 2). This is in line with the published rat dendrin protein size (81 kD) (30).…”

Section: Dendrinsupporting

confidence: 91%

“…Dendrin is an intracellular protein without known motifs or function (30,31). RT-PCR and Northern blotting experiments demonstrated the presence of dendrin transcript in brain, kidney, and lung tissues (Figure 1).…”

Section: Dendrinmentioning

confidence: 99%

Expression and Subcellular Distribution of Novel Glomerulus-Associated Proteins Dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik

Patrakka¹,

Xiao²,

Nukui³

et al. 2007

Journal of the American Society of Nephrology

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“…A full-length cDNA clone of rat dendrin (52) was cloned in frame into a modified pGEX vector, pEGFP-C1 (BD Bioscience Clontech, San Jose, CA), or pFLAG-CMV-5c (Sigma-Aldrich, St. Louis, MO). The N-terminal (amino acids 1-351) and C-terminal (amino acids 352-653) fragments of dendrin were generated by PCR and cloned into pEGFP-C1.…”

Section: Methodsmentioning

confidence: 99%

Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes

Asanuma

Campbell

Kim

et al. 2007

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

126

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Kidney podocytes and their slit diaphragms (SDs) form the final barrier to urinary protein loss. There is mounting evidence that SD proteins also participate in intracellular signaling pathways. The SD protein nephrin serves as a component of a signaling complex that directly links podocyte junctional integrity to actin cytoskeletal dynamics. Another SD protein, CD2-associated protein (CD2AP), is an adaptor molecule involved in podocyte homeostasis that can repress proapoptotic TGF-␤ signaling in podocytes. Here we show that dendrin, a protein originally identified in telencephalic dendrites, is a constituent of the SD complex, where it directly binds to nephrin and CD2AP. In experimental glomerulonephritis, dendrin relocates from the SD to the nucleus of injured podocytes. High-dose, proapoptotic TGF-␤1 directly promotes the nuclear import of dendrin, and nuclear dendrin enhances both staurosporine-and TGF-␤1-mediated apoptosis. In summary, our results identify dendrin as an SD protein with proapoptotic signaling properties that accumulates in the podocyte nucleus in response to glomerular injury and provides a molecular target to tackle proteinuric kidney diseases. Nuclear relocation of dendrin may provide a mechanism whereby changes in SD integrity could translate into alterations of podocyte survival under pathological conditions. glomerular injury ͉ proapoptotic signaling ͉ TGF-␤ signaling ͉ slit diaphragm G lomerular podocytes serve as the final barrier to urinary protein loss by the formation and maintenance of podocyte foot processes (FP) and the interposed slit diaphragm (SD) (1). All forms of nephrotic syndrome are characterized by abnormalities in podocytes, including retraction (effacement) of podocyte FP and/or molecular reorganization of the SD (1). The discovery of several podocyte proteins and their mutation analysis, including nephrin (2), CD2-associated protein (CD2AP) (3), ␣-actinin-4 (4), podocin (5), TRPC6 (6, 7), and neph1 (8), have shed light on the pathogenesis of proteinuria and emphasized the critical role of the podocyte and the SD in maintaining the function of the glomerular filtration barrier. At the cytoplasmic insertion site of the SD, ZO-1 (9), ␣-, ␤-, ␥-catenins (10), podocin (11), and CD2AP (3) are present. In nephrotic syndrome, the normal podocyte substructure is lost, with effacement of podocyte FP, proteinuria (1), as well as altered phosphorylation of ZO-1 (12) and nephrin (13,14).Dendrin is a proline-rich protein of unknown function that was originally identified in telencephalic dendrites of sleep-deprived rats (15). In the brain, two protein variants (81 kDa, 89 kDa) were identified in cytosolic and membranous protein fractions (15). More recently, KIBRA, a WW domain-containing protein, was identified as a dendrin-interacting protein, but the functional relevance of this interaction remains to be established (16). Here we show that dendrin is a component of the SD complex. We further show that dendrin relocates to the nucleus of injured podocytes in a murine model of cr...

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“…The dendritic trafficking of this transcript and the role of local translated CaMKIIa in synaptic plasticity events has been widely studied (Mayford et al, 1996;Miller et al, 2002;Ouyang et al, 1999). Other relatively abundant mRNAs in the neuropil region included the transcripts encoding for Shank1, PSD95 (postsynaptic density protein 95), Dendrin and MAP (microtubule-associated protein) 1A (Cajigas et al, 2012), all of them previously reported as dendritic mRNAs (Bockers et al, 2004;Herb et al, 1997;Muddashetty et al, 2007;Tucker et al, 1989).…”

Section: Cis-acting Elements and Mrna Transport Into Dendritesmentioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

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a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

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Prominent Dendritic Localization in Forebrain Neurons of a Novel mRNA and Its Product, Dendrin

Cited by 65 publications

References 27 publications

Expression and Subcellular Distribution of Novel Glomerulus-Associated Proteins Dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik

Expression and Subcellular Distribution of Novel Glomerulus-Associated Proteins Dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik

Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes

BDNF-induced local protein synthesis and synaptic plasticity

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