Palladin is aprotein that in humans is encoded by thePALLDgene.[5][6][7][8] Palladin is a component ofactin-containing microfilaments that control cell shape,adhesion, and contraction.[8]
Palladin was characterised independently by two research groups, first in the lab of Carol Otey (in 2000)[6] and then in the lab of Olli Carpén (in 2001).[9] It is a part of the myotilin-myopalladin-palladin family and may play an important role in modulating theactincytoskeleton.[10] Palladin, in contrast tomyotilin andmyopalladin, which are expressed only instriated muscle, is expressed ubiquitously in cells ofmesenchymal origin.
Palladin was named after the Italian Renaissance architectAndrea Palladio, reflecting its localization to architectural elements of the cell.[6]
The eukaryotic cytoskeleton. Palladin is one component of this complex cellular machinery.
In humans, it appears that seven different isoforms exist, some of which arise throughalternative splicing.[11] 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.[6]
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.[10]
Recently, it has been demonstrated that palladinRNA is overexpressed in patients withpancreaticneoplasia, and that palladin is both overexpressed and mutated in an inherited form ofpancreatic cancer.[12] 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.[13][14]
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,[15] suggesting that palladin's role in this disease may involve changes in the tumor microenvironment. 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 inmyopalladin cause an inherited form of heart disease (dilated cardiomyopathy).
^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.S2CID2445261.
King CM, Olive CW, Cardona RA (1975). "Activation of carcinogenic arylhydroxamic acids by human tissues".J. Natl. Cancer Inst.55 (2):285–7.doi:10.1093/jnci/55.2.285.PMID1159819.
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.
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.S2CID14294292.
