Palladin is a protein that in humans is encoded by the PALLDgene.[1][2][3][4] Palladin is a component of actin-containing microfilaments that control cell shape, adhesion, and contraction.[4]
Palladin was characterised independently by two research groups, first in the lab of Carol Otey (in 2000)[2] and then in the lab of Olli Carpén (in 2001).[5] It is a part of the myotilin-myopalladin-palladin family and may play an important role in modulating the actincytoskeleton.[6] Palladin, in contrast to myotilin and myopalladin, which are expressed only in striated muscle, is expressed ubiquitously in cells of mesenchymal origin.
Palladin was named after the Renaissance architect Andrea Palladio, reflecting its localization to architectural elements of the cell.[2]
The eukaryotic cytoskeleton. Palladin is one component of this complex cellular machinery.
Isoforms
In humans, it appears that seven different isoforms exist, some of which arise through alternative splicing.[7] In mice, three major isoforms of palladin arise from a single gene. These isoforms contain between three and five copies (depending on the isoform) of an Ig-like domain and between one and two copies of a polyproline domain.[2]
Function
Palladin's precise biological role is poorly understood, but it has been shown to play a role in cytoskeletal organization, embryonic development, cell motility, scar formation in the skin, and nerve cell development.[6]
Disease linkage
Recently, it has been demonstrated that palladin RNA is overexpressed in patients with pancreaticneoplasia, and that palladin is both overexpressed and mutated in an inherited form of pancreatic cancer.[8] The palladin mutation identified in familial pancreatic cancer may be unique to a single North American family, as this same mutation has not been found in any other European or North American populations, respectively, in two other genetic studies.[9][10]
Further, Salaria et al. have shown that palladin is overexpressed in the non-neoplastic stroma of pancreatic cancer, but only rarely in the cancer cells per se,[11] suggesting that palladin's role in this disease may involve changes in the tumor microenvironmment. More research is clearly required before this protein and its role in neoplasia can be fully understood.
Disease-causing mutations have also been identified in the two other members of this gene family. Myotilin mutations cause a form of limb-girdle muscular dystrophy, and mutations in myopalladin cause an inherited form of heart disease (dilated cardiomyopathy).
↑Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID10231032.
↑ 6.06.1Otey CA, Rachlin A, Moza M, Arneman D, Carpen O (2005). The palladin/myotilin/myopalladin family of actin-associated scaffolds. Int. Rev. Cytol. International Review of Cytology. 246. pp. 31–58. doi:10.1016/S0074-7696(05)46002-7. ISBN9780123646507. PMID16164966.
↑Rachlin AS, Otey CA (2006). "Identification of palladin isoforms and characterization of an isoform-specific interaction between Lasp-1 and palladin". J. Cell Sci. 119 (Pt 6): 995–1004. doi:10.1242/jcs.02825. PMID16492705.
↑Zogopoulos G, Rothenmund H, Eppel A, Ash C, Akbari MR, Hedley D, Narod SA, Gallinger S (2007). "The P239S palladin variant does not account for a significant fraction of hereditary or early onset pancreas cancer". Hum. Genet. 121 (5): 635–7. doi:10.1007/s00439-007-0361-z. PMID17415588.
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Moriyama K, Bonifacino JS (2003). "Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles". Traffic. 3 (9): 666–77. doi:10.1034/j.1600-0854.2002.30908.x. PMID12191018.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Rönty M, Taivainen A, Moza M, et al. (2004). "Molecular analysis of the interaction between palladin and alpha-actinin". FEBS Lett. 566 (1–3): 30–4. doi:10.1016/j.febslet.2004.04.006. PMID15147863.
Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4". Nature. 434 (7034): 724–31. doi:10.1038/nature03466. PMID15815621.
Rönty M, Taivainen A, Moza M, et al. (2005). "Involvement of palladin and alpha-actinin in targeting of the Abl/Arg kinase adaptor ArgBP2 to the actin cytoskeleton". Exp. Cell Res. 310 (1): 88–98. doi:10.1016/j.yexcr.2005.06.026. PMID16125169.
Boukhelifa M, Moza M, Johansson T, et al. (2006). "The proline-rich protein palladin is a binding partner for profilin". FEBS J. 273 (1): 26–33. doi:10.1111/j.1742-4658.2005.05036.x. PMID16367745.
Rönty MJ, Leivonen SK, Hinz B, et al. (2007). "Isoform-specific regulation of the actin-organizing protein palladin during TGF-beta1-induced myofibroblast differentiation". J. Invest. Dermatol. 126 (11): 2387–96. doi:10.1038/sj.jid.5700427. PMID16794588.
Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID16964243.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
