Disease relevance of Synpo

• Here we show that synpo(-/-) mice display impaired recovery from protamine sulfate-induced podocyte foot process (FP) effacement and LPS-induced nephrotic syndrome [1].
• Nephrotic-range proteinuria was observed already at 2 wk, together with dedifferentiation and dysregulation of podocytes, indicated by decreased expression of nephrin, synaptopodin, and Wilms' tumor 1 protein and increased expression of Ki-67 [2].
• Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model [3].
• Suppression of HIV-1 transcription by flavopiridol or roscovitine was marked by re-expression of the podocyte differentiation markers, synaptopodin and podocalyxin [4].
• CONCLUSIONS: We conclude that down-regulation of nephrin and synaptopodin is associated with proteinuria in women with preeclampsia [5].
• Bigenic heterozygosity for synaptopodin and CD2AP is sufficient to induce spontaneous proteinuria and focal segmental glomerulosclerosis-like glomerular damage in mice [6].

High impact information on Synpo

• In contrast, the ultrastructure of podocytes in synpo(-/-) mice is normal [1].
• Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner [1].
• Synaptopodin-deficient (synpo(-/-)) mice lack the dendritic spine apparatus and display impaired activity-dependent long-term synaptic plasticity [1].
• Similarly, synpo(-/-) podocytes show impaired actin filament reformation in vitro [1].
• Gene silencing of Synpo-T abrogates stress-fiber formation in synpo(-/-) podocytes, demonstrating that Synpo-T serves as a backup for Synpo-long in synpo(-/-) podocytes [1].

Biological context of Synpo

• To test this hypothesis, synaptopodin was studied in the cortex, striatum, and hippocampus of normal and reeler mice, in which developmental cell migration defects have disrupted the normal array of cells [7].
• Both compounds inhibited cell proliferation significantly and restored synaptopodin expression in HIV-infected podocytes [8].

Anatomical context of Synpo

• Synaptopodin and 4 novel genes identified in primary sensory neurons [9].
• Expression of 4930579P15Rik and synaptopodin was restricted to craniospinal sensory ganglia [9].
• Synaptopodin puncta located within dendrites of principal neurons were primarily found in spines (>95%) [10].
• To learn more about the cellular basis underlying this distribution, the regional, laminar, and cellular localization of Synaptopodin and its mRNA were analyzed in mouse hippocampus [10].

Associations of Synpo with chemical compounds

• Synaptopodin is the founding member of a novel class of proline-rich actin-associated proteins highly expressed in telencephalic dendrites and renal podocytes [1].
• Treatment with atRA reduced cell proliferation rate by causing G1 arrest and restored the expression of the differentiation markers (synaptopodin, nephrin, podocin, and WT-1) in HIV-1-infected podocytes [8].

Other interactions of Synpo

• Neither synaptopodin, nor any known family member of 4930579P15Rik, has ever been described in sensory neurons [9].
• To confirm the precise localization and developmental changes of EPO-R expression in podocytes in mature and developing glomeruli, we examined co-expression with the podocyte markers WT-1 and synaptopodin [11].
• Myosin II, alpha-actinin, and the podocyte-specific protein synaptopodin were present in radial SF, but, opposite to F-actin, they were not enriched in the ARC [12].
• These changes are accompanied by loss of the maturation markers synaptopodin and WT1, and expression of the proliferation marker Ki-67 [13].
• Intriguingly, nephrin and actin-associated proteins (synaptopodin, CD2AP, and cortactin) were recruited to and accumulated at the entire cell margin only in confluent cells, but not in dispersed cells [14].

Analytical, diagnostic and therapeutic context of Synpo

• First, Synaptopodin puncta densities were quantified after immunofluorescent labeling using confocal microscopy [10].
• Finally, synaptopodin mRNA expression was studied using in situ hybridization, laser microdissection, and quantitative reverse transcriptase-polymerase chain reaction [10].

References