Disease relevance of SYNPO

• Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers [1].
• In contrast, in collapsing idiopathic FSGS and HIV-associated nephropathy, there was disappearance of all markers from all collapsed glomeruli and of synaptopodin from 16% of noncollapsed glomeruli [2].
• (2) In the cellular variant, most podocytes had lost podocyte-specific epitopes (podocalyxin, synaptopodin, glomerular epithelial protein-1, Wilm's tumor protein-1, complement receptor-1, and vimentin) [3].
• Synaptopodin expression in idiopathic nephrotic syndrome of childhood [4].
• We found that HIV-1 nef was necessary and sufficient for proliferation of podocytes and down-regulation of synaptopodin and CALLA [5].

High impact information on SYNPO

• Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling [6].
• Gene silencing of synaptopodin in kidney podocytes causes the loss of stress fibres and the formation of aberrant non-polarized filopodia and impairment of cell migration [6].
• Synaptopodin is an actin-associated protein of differentiated podocytes that also occurs as part of the actin cytoskeleton of postsynaptic densities (PSD) and associated dendritic spines in a subpopulation of exclusively telencephalic synapses [7].
• In both brain and kidney, in vivo and in vitro, synaptopodin gene expression is differentiation dependent [7].
• The open reading frame of synaptopodin encodes a polypeptide with a calculated Mr of 73.7 kD (human)/74.0 kD (mouse) and an isoelectric point of 9.38 (human)/9 [7].

Chemical compound and disease context of SYNPO

• CONCLUSIONS: We conclude that down-regulation of nephrin and synaptopodin is associated with proteinuria in women with preeclampsia [8].

Biological context of SYNPO

• Amino acid sequences determined in purified rat kidney and forebrain synaptopodin and derived from human and mouse brain cDNA clones show no significant homology to any known protein [7].
• Together, these data show that synaptopodin is essential for the integrity of the podocyte actin cytoskeleton and for the regulation of podocyte cell migration [6].
• Postictal upregulation of Synaptopodin mRNA levels in target cell populations of limbic epilepsy-elicited damage and subsequent Synaptopodin protein expression largely co-localized with remodeling processes as demonstrated by mossy fiber sprouting [9].
• Moreover, Tat deregulated the podocyte phenotype causing down-regulation of maturity markers such as WT-1 and synaptopodin, alteration of cytoarchitecture, and impairment of permselectivity [10].
• Both compounds inhibited cell proliferation significantly and restored synaptopodin expression in HIV-infected podocytes [11].

Anatomical context of SYNPO

• Synaptopodin (SYNPO) is a cytoskeletal protein that is preferentially located in mature dendritic spines, where it accumulates in the spine neck and closely associates with the spine apparatus [12].
• We postulated that in Galloway-Mowat syndrome the mutation would be in a protein that is expressed both in podocytes and neurons, such as synaptopodin, GLEPP1, or nephrin [13].
• From these results and experiments with cultured cells we conclude that synaptopodin represents a novel kind of proline-rich, actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and podocyte foot processes [7].
• Expression of synaptopodin, an actin-associated protein, in the rat hippocampus after limbic epilepsy [9].
• Synaptopodin immunoreactivity in the dendritic layers of CA3, in the hilus and in the inner molecular layer of the dentate gyrus (DG) was initially reduced [9].

Associations of SYNPO with chemical compounds

• Synaptopodin, GLEPP1, and nephrin were strongly expressed in normal kidney tissue [13].
• Synaptopodin contains a high amount of proline ( approximately 20%) equally distributed along the protein, thus virtually excluding the formation of any globular domain [7].
• Eight weeks after KA treatment Synaptopodin protein expression returned to control levels in dendritic layers of CA3 and in the entire molecular layer of the DG [9].
• Greater synaptopodin expression in podocytes was associated with a significantly better response to steroid therapy (P < 0.05 for both L and A) [4].
• A significant reduction, however, was only seen for synaptopodin immunoreactivity in stratum oriens and pyramidale of hippocampal CA1 subfield [14].

Other interactions of SYNPO

• MAGI-1 and synaptopodin can also interact in vivo, as they can be immunoprecipitated together from HEK293 cell lysates [15].
• NEPH1 and synaptopodin expression was detected only at the mRNA level [16].
• When exposed to all nephrotic plasma samples (and a non-human serum control), nephrin podocin and CD2AP assumed a cytoplasmic distribution; nephrin and synaptopodin were selectively downregulated, and the relocation of nephrin induced by nephrotic plasma could be rescued back to the plasma membrane by co-incubation with non-nephrotic plasma [17].
• Moreover, there was partial loss of synaptopodin and cyclin D1 expression in nonaffected glomeruli [18].
• Hippocampi with neuronal densities comparable to those of sham-operated control animals were analyzed for dendritic marker proteins MAP2, MAP1B and synaptopodin, respectively [14].

Analytical, diagnostic and therapeutic context of SYNPO

• During postnatal maturation of rat brain, synaptopodin is first detected by Western blot analysis at day 15 and reaches maximum expression in the adult animal [7].
• Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation [1].
• METHODS: Immunohistochemistry was performed for synaptopodin expression on renal tissues from MCD (N = 18), DMH (N = 7), FSGS (N = 13), CNF (N = 9), and normal children (N = 7) [4].
• To study whether synaptopodin and the spine apparatus organelle are regulated under conditions of lesion-induced plasticity, synaptopodin and the spine apparatus were analyzed in granule cells of the rat fascia dentata following entorhinal denervation [19].
• CONCLUSIONS: The increased permeability of the filtration barrier in steroid-resistant glomerulopathies may be a consequence of subcellular changes in podocytes resulting from decreased expression of synaptopodin [20].

References