Disease relevance of Pfn1

• Enhanced glomerular profilin gene and protein expression in experimental mesangial proliferative glomerulonephritis [1].
• We used a rat model of mesangial proliferative nephritis induced with antibody to the Thy 1 antigen present on mesangial cells to investigate whether profilin is upregulated [1].

Psychiatry related information on Pfn1

• We propose that profilin may act by forming, during the critical period of cerebellar development, a reserve pool of monomeric actin that can easily be mobilized in cell regions such as growth cones or synaptic junctions where filamentous actin is highly concentrated [2].

High impact information on Pfn1

• To test this hypothesis we examined the effect of ATP depletion induced by antimycin A and substrate depletion on actin polymerization, the nucleotide state of the monomer pool, and the association of actin monomers with thymosin and profilin in the kidney epithelial cell line LLC-PK1 [3].
• Targeting of this SNARE to the ykt6 compartment was mediated by its profilin-like amino-terminal domain, even in the absence of protein prenylation [4].
• Production of PIP and PIP2 may be important downstream signals since these polyphosphoinositides are able to regulate the interaction of gelsolin and profilin with actin [5].
• In cultured rat mesangial cells, expression of profilin mRNA and protein was upregulated by basic fibroblast growth factor but not by platelet-derived growth factor or transforming growth factor-beta [6].
• Expression of profilin, an actin-binding protein, in rat experimental glomerulonephritis and its upregulation by basic fibroblast growth factor in cultured rat mesangial cells [6].

Biological context of Pfn1

• Experimental depolarization of epithelial cells results in the loss of normal F-actin structures and the transient upregulation of vinculin, VASP, and profilin [7].
• Thus, vinculin, VASP, and profilin are coordinately regulated by signal transduction pathways that effect a translational response [7].
• Profilin binds to actin monomer to regulate actin polymerization, and to phosphatidylinositol 4,5-bisphosphate to inhibit hydrolysis by phospholipase Cgamma1 [6].
• This simultaneous targeting to dendritic spines and the cell nucleus suggests a novel mechanism of neuronal plasticity in which profilin both tags activated synapses and influences nuclear events [8].
• A transient increase of profilin mRNA and profilin was observed at the end of the first postnatal week, a period of intense cell proliferation, neuritic outgrowth and synaptogenesis [2].

Anatomical context of Pfn1

• Vinculin, VASP, and profilin are coordinately regulated during actin remodeling in epithelial cells, which requires de novo protein synthesis and protein kinase signal transduction pathways [7].
• These results suggest that profilin may be involved in the pathogenesis of glomerulonephritis by reorganizing actin cytoskeleton [1].
• Immunoelectron microscopy revealed the presence of profilin in plasma membrane and the rough endoplasmic reticulum of mesangial cells, indicating that profilin was produced in mesangial cells [6].
• Distribution of profilin in fibroblasts correlates with the presence of highly dynamic actin filaments [9].
• It is also possible that PtdIns-4,5-P2 has other roles, such as promoting the release of G actin from profilin or promoting the cross-linking of actin or its anchorage to the plasma membrane [10].

Associations of Pfn1 with chemical compounds

• Profilin and actin mRNA increased after acute and chronic treatments of carbon tetrachloride, which is associated with the increase of fibronectin, type-III and -IV collagen mRNA [11].
• Profilin represented nearly 0.1% of total Triton-soluble protein both at birth and at the end of the developmental period [2].
• The concentration of profilin mRNA decreased in dBcAMP-reactive astrocytes (-46%) [12].
• Pretreatment with 1 microM BFA increased the PIP2 signal on profilin-1 x 54% after 15 mins, followed by a decline to subbasal levels after 60 mins [13].

Regulatory relationships of Pfn1

• These studies identify a previously unrecognized oxysterol-binding protein-mediated mode of activation of STAT3 that controls the expression of the proatherogenic protein profilin-1 in response to 7-ketocholesterol and the diabetic milieu [14].

Other interactions of Pfn1

• Here we show that following NMDA receptor activation profilin also accumulates in the nucleus of hippocampal neurons via a process involving rearrangement of the actin cytoskeleton [8].
• Furthermore, a simultaneous expression of profilin, actin and extracellular matrix proteins was observed during the regeneration of rat liver, that is, all mRNAs of these proteins showed biphasic peaks around 6 h and 48 h after partial hepatectomy [11].
• Endothelin-1 mobilizes profilin-1-bound PIP2 in cardiac muscle [13].

Analytical, diagnostic and therapeutic context of Pfn1

• We amplified and sequenced rat profilin cDNA by the reverse-transcribed-polymerase chain reaction (RT-PCR) [1].
• At 7 days after disease induction, enhanced expression in both profilin mRNA and protein was demonstrated in the isolated glomeruli by RT-PCR and Western blot analysis [1].
• Increased expression of profilin protein was confirmed using immunoblotting and immunohistochemistry [6].
• Immunofluorescence of whole cells and immunogold labeling on ventral membranes of lysis-squirted cells showed that profilin was markedly enriched in the highly dynamic lamellipodia or pseudopodial lobes [9].
• 12K protein was separated into two components, 12K-1 (larger) and 12K-2 (smaller), by gel chromatography which had similar amino acid compositions to those of profilin (from Acanthamoeba and hog thyroid) [15].

References