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Pfn1  -  profilin 1

Mus musculus

Synonyms: Pfn, Profilin I, Profilin-1, actin binding protein
 
 
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Disease relevance of Pfn1

  • The association of Mena with the surface of the intracellular pathogen Listeria monocytogenes and the G-actin binding protein profilin suggests that this molecule may participate in bacterial movement by facilitating actin polymerization [1].
  • Profilin is a small actin-binding protein that is involved in diverse functions such as maintaining cell structure integrity, cell mobility, tumor cell metastasis, as well as growth factor signal transduction [2].
  • Support for this premise is found in in vivo studies of mouse kidney fibroblasts which demonstrated increased translocational locomotion after cytoplasmic gelsolin expression was increased genetically and in melanoma cells missing actin-binding protein which behave as expected for a cell unable to achieve efficient actin gelation [3].
  • We previously identified an actin-binding protein, actinin-4, as a new biomarker of cancer invasion and an indicator of prognosis for patients with breast cancer [4].
  • We have shown, using purified proteins and cell extracts, that MIM-B is an actin-binding protein, probably via a WASP (Wiskott-Aldrich syndrome protein)-homology 2 domain at its C-terminus [5].
 

High impact information on Pfn1

  • Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis [6].
  • Gelsolin, an 82 kDa actin-binding protein, has potent actin filament-severing activity in vitro [7].
  • Increasing the content of the actin-binding protein gelsolin in cultured mouse fibroblasts by up to 125 percent by gene transfection proportionally enhanced the rate at which the cells migrated through porous filters toward a gradient of serum and closed a wound made on a confluent monolayer of cells in a tissue culture dish [8].
  • Activity-induced targeting of profilin and stabilization of dendritic spine morphology [9].
  • Using primary neurons expressing GFP-tagged proteins, we found that profilin, a regulator of actin polymerization, is targeted to spine heads when postsynaptic NMDA receptors are activated and that actin-based changes in spine shape are concomitantly blocked [9].
 

Chemical compound and disease context of Pfn1

 

Biological context of Pfn1

 

Anatomical context of Pfn1

 

Associations of Pfn1 with chemical compounds

 

Physical interactions of Pfn1

 

Regulatory relationships of Pfn1

  • Antisense knockdown of profilin I and II isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN and its associated proteins in cytoplasmic aggregates [22].
 

Other interactions of Pfn1

 

Analytical, diagnostic and therapeutic context of Pfn1

  • Northern blot analysis showed that transcript of profilin was upregulated in a transient manner in the deafferented rat hippocampus by 1.5-, 1.9-, 1.4-, and 1.1-fold of controls, respectively, at 1, 3, 7, and 15 days post-lesion [14].
  • Profilin targeting was triggered by electrical stimulation patterns known to induce the long-term changes in synaptic responsiveness associated with memory formation [9].
  • Immune electron microscopy of dry and rehydrated birch pollens showed that after short hydration, the major birch pollen allergen, Bet v I, migrated into the exine and to the surface of intact pollen grains, whereas profilin, against which a lower percentage of patients is sensitized, was retained in the pollen grain [26].
  • RT-PCR analysis of mouse profilin cDNA from tsFT101 showed a point mutation (177 A two head right arrow G) which was a wobble mutation causing no change in the encoded amino acid [27].
  • At least two different antigenic determinants were recognized in H. annuus profilin by immunoblotting [28].

References

  1. Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics. Gertler, F.B., Niebuhr, K., Reinhard, M., Wehland, J., Soriano, P. Cell (1996) [Pubmed]
  2. Molecular cloning and characterization of profilin-3: a novel cytoskeleton-associated gene expressed in rat kidney and testes. Hu, E., Chen, Z., Fredrickson, T., Zhu, Y. Exp. Nephrol. (2001) [Pubmed]
  3. Actin structural proteins in cell motility. Cunningham, C.C. Cancer Metastasis Rev. (1992) [Pubmed]
  4. Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer. Honda, K., Yamada, T., Hayashida, Y., Idogawa, M., Sato, S., Hasegawa, F., Ino, Y., Ono, M., Hirohashi, S. Gastroenterology (2005) [Pubmed]
  5. MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta. Woodings, J.A., Sharp, S.J., Machesky, L.M. Biochem. J. (2003) [Pubmed]
  6. Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Romero, S., Le Clainche, C., Didry, D., Egile, C., Pantaloni, D., Carlier, M.F. Cell (2004) [Pubmed]
  7. Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin. Witke, W., Sharpe, A.H., Hartwig, J.H., Azuma, T., Stossel, T.P., Kwiatkowski, D.J. Cell (1995) [Pubmed]
  8. Enhanced motility in NIH 3T3 fibroblasts that overexpress gelsolin. Cunningham, C.C., Stossel, T.P., Kwiatkowski, D.J. Science (1991) [Pubmed]
  9. Activity-induced targeting of profilin and stabilization of dendritic spine morphology. Ackermann, M., Matus, A. Nat. Neurosci. (2003) [Pubmed]
  10. Overexpression of Nd1, a novel Kelch family protein, in the heart of transgenic mice protects against doxorubicin-induced cardiomyopathy. Matsudo, Y., Takamori, Y., Fujimura, L., Nishio, S., Sasagawa, K., Komuro, I., Tokuhisa, T., Hatano, M. Transgenic Res. (2006) [Pubmed]
  11. Profilin I is essential for cell survival and cell division in early mouse development. Witke, W., Sutherland, J.D., Sharpe, A., Arai, M., Kwiatkowski, D.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. Accumulation of profilin II at the surface of Listeria is concomitant with the onset of motility and correlates with bacterial speed. Geese, M., Schlüter, K., Rothkegel, M., Jockusch, B.M., Wehland, J., Sechi, A.S. J. Cell. Sci. (2000) [Pubmed]
  13. The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis. Crowley, M.R., Head, K.L., Kwiatkowski, D.J., Asch, H.L., Asch, B.B. Dev. Biol. (2000) [Pubmed]
  14. Entorhinal deafferentation induces the expression of profilin mRNA in the reactive microglial cells in the hippocampus. Dong, J.H., Ying, G.X., Zhou, C.F. Glia (2004) [Pubmed]
  15. The actin-binding protein profilin I is localized at synaptic sites in an activity-regulated manner. Neuhoff, H., Sassoè-Pognetto, M., Panzanelli, P., Maas, C., Witke, W., Kneussel, M. Eur. J. Neurosci. (2005) [Pubmed]
  16. The actin-binding protein UNC-115/abLIM controls formation of lamellipodia and filopodia and neuronal morphogenesis in Caenorhabditis elegans. Yang, Y., Lundquist, E.A. Mol. Cell. Biol. (2005) [Pubmed]
  17. Upregulation of cortactin expression during the maturation of megakaryocytes. Zhan, X., Haudenschild, C.C., Ni, Y., Smith, E., Huang, C. Blood (1997) [Pubmed]
  18. Differential phospholipase D activation by bradykinin and sphingosine 1-phosphate in NIH 3T3 fibroblasts overexpressing gelsolin. Banno, Y., Fujita, H., Ono, Y., Nakashima, S., Ito, Y., Kuzumaki, N., Nozawa, Y. J. Biol. Chem. (1999) [Pubmed]
  19. Functional characterization of green fluorescent protein-profilin fusion proteins. Wittenmayer, N., Rothkegel, M., Jockusch, B.M., Schlüter, K. Eur. J. Biochem. (2000) [Pubmed]
  20. Molecular and structural analysis of a continuous birch profilin epitope defined by a monoclonal antibody. Wiedemann, P., Giehl, K., Almo, S.C., Fedorov, A.A., Girvin, M., Steinberger, P., Rüdiger, M., Ortner, M., Sippl, M., Dolecek, C., Kraft, D., Jockusch, B., Valenta, R. J. Biol. Chem. (1996) [Pubmed]
  21. Mena is required for neurulation and commissure formation. Lanier, L.M., Gates, M.A., Witke, W., Menzies, A.S., Wehman, A.M., Macklis, J.D., Kwiatkowski, D., Soriano, P., Gertler, F.B. Neuron (1999) [Pubmed]
  22. A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells. Sharma, A., Lambrechts, A., Hao, l.e. .T., Le, T.T., Sewry, C.A., Ampe, C., Burghes, A.H., Morris, G.E. Exp. Cell Res. (2005) [Pubmed]
  23. Localization of profilin-1 (Pfn1) and a related sequence (Pfn1-rs) to mouse chromosomes 11 and 15 respectively. Klingenspor, M., Bodnar, J., Xia, Y.R., Welch, C., Lusis, A.J., Reue, K. Mamm. Genome (1997) [Pubmed]
  24. Purification and expression of gCap39. An intracellular and secreted Ca2(+)-dependent actin-binding protein enriched in mononuclear phagocytes. Johnston, P.A., Yu, F.X., Reynolds, G.A., Yin, H.L., Moomaw, C.R., Slaughter, C.A., Südhof, T.C. J. Biol. Chem. (1990) [Pubmed]
  25. Neutrophils lacking platelet-endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2-mediated chemotaxis. Wu, Y., Stabach, P., Michaud, M., Madri, J.A. J. Immunol. (2005) [Pubmed]
  26. Properties of tree and grass pollen allergens: reinvestigation of the linkage between solubility and allergenicity. Vrtala, S., Grote, M., Duchêne, M., van Ree, R., Kraft, D., Scheiner, O., Valenta, R. Int. Arch. Allergy Immunol. (1993) [Pubmed]
  27. Profilin gene expression and regulation in a temperature-sensitive breast cancer cell line: tsFT101. Cao, Y., Motomura, K., Ohtsuru, A., Matsumoto, T., Yamashita, S., Kosaka, M. Pflugers Arch. (1997) [Pubmed]
  28. Production and characterization of profilin monoclonal antibodies. Arilla, M.C., Asturias, J.A., Gómez-Bayón, N., Martínez, A., Martínez, J., Palacios, R. Allergologia et immunopathologia. (1997) [Pubmed]
 
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