DDN

Official Full Name

dendrin

Organism

Homo sapiens

GeneID

23109

Background

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cell projection and cytoplasm. [provided by Alliance of Genome Resources, Feb 2025]

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Detailed Information

Dendrin is a novel protein first identified in neurons of the rat. It was thought not to be expressed out- side the brain. It encodes a cytoplasmic protein that functions as a scaffolding molecule, playing a pivotal role in shaping the architecture of neurons and their synaptic connections. Dendrin also in the podocytes of the glomerulus. Podocytes represent only a very small portion of renal cells, and therefore dendrin expression is hard to detect in whole kidney fractions.

Gene Structure and Expression of Ddn

The Ddn gene is located on the X chromosome in mammals and is composed of 17 exons. It spans approximately 80 kb and is flanked by two CpG islands, suggesting the presence of regulatory elements that control its expression. The Ddn gene is expressed in various tissues, including the brain, heart, liver, and skeletal muscle, but its expression is particularly prominent in the nervous system.

Ddn Plays A Role in Glomerular Action

Dendrin is hydrophilic but has no potential transmembrane region. In neurons, it interacts with the cytoskeletal protein alpha-actinin, which may imply its importance for cell shape. one of the four isoforms of alpha-actinin is expressed in glomerular podocytes to bundle and possibly organize their actin cytoskeleton. However, the function of dendrin in normal glomeruli and its potential role in disease are unknown. It has been hypothesized that dendrin may be another important player in this dramatic change in cell shape of the FPE, and thus in proteinuria. If dendrin plays a key role in the pathogenesis of MCNS, we would have expected a substantial loss of dendrin gold markers. However, there is no support for such a dramatic effect. There was no change in the amount of dendrin in the preserved clefts. Furthermore, in the absence of dendrin expression was unchanged compared to controls. compared to controls. Therefore, it is believed that the redistribution of dendrin and ZO-1 is a secondary phenomenon of FPE, the cause of which has not been identified.

Ddn plays a role in glomerulogenesis

During glomerulogenesis, dendrin mRNA and protein first appear in the early stages of capillary loops. It is concentrated in anterior nodal cells on the basolateral side of the apical cell membrane marker podocalyxin. In human tissues, dendrin transcripts were detected in the brain and kidney. In the mature kidney, dendrin is localized only in podocalyxin cells near the filtration slit septum. In minimal change nephrotic syndrome (MCNS), dendrin was compared to the filtration slit-associated protein Zonula occludens-1 (ZO-1). In the region of pedunculated prolapse (FPE), dendrin and ZO-1 were redistributed from the slit region to the podocyte cytoplasm. There was no change in the distribution of dendrin and ZO-1 in the FPE-free region compared with controls.

Figure 1. Kibra Modulates Learning and Memory via Binding to Dendrin

The Ddn (dendrin) plays a pivotal role in shaping the architecture of neurons and their synaptic connections. Mutations in the Ddn gene have been implicated in various neurological disorders, highlighting the importance of understanding its function in neural development and synaptic plasticity.

References:

Coppo R, Fervenza FC. Dendrin in IgA nephropathy: protective or marker of early disease? Nephrol Dial Transplant. 2023 Feb 13;38(2):261-263. doi: 10.1093/ndt/gfac258. PMID: 36073761.
Levin A, Schwarz A, Hulkko J, He L, Sun Y, Barany P, Bruchfeld A, Herthelius M, Wennberg L, Ebefors K, Patrakka J, Betsholtz C, Nyström J, Mölne J, Hultenby K, Witasp A, Wernerson A. The role of dendrin in IgA nephropathy. Nephrol Dial Transplant. 2023 Feb 13;38(2):311-321. doi: 10.1093/ndt/gfac208. PMID: 35767852; PMCID: PMC9923709.
Dunér F, Patrakka J, Xiao Z, et al. Dendrin expression in glomerulogenesis and in human minimal change nephrotic syndrome. Nephrol Dial Transplant. 2008;23(8):2504-2511. doi:10.1093/ndt/gfn100

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