Palladin

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This article is about a protein. For information about the rank, see paladin.
The eukaryotic cytoskeleton. Palladin is one component of this complex cellular machinery.
KIAA0922
Identifiers
Symbol KIAA0922
Alt. Symbols DKFZp586H1322, TMEM131L
Entrez 23240
HUGO 29146
RefSeq NM_015196
UniProt A2VDJ0
Other data
Locus Chr. 4 q31.3

Palladin protein is a cytoskeletal protein coded by the palladin gene (KIAA0992).[1][2] Palladin was characterised independently by two research groups, first in the lab of Carol Otey (in 2000)[3] and then in the lab of Olli Carpén (in 2001).[4] It is a part of the myotilin-myopalladin-palladin family and may play an important role in modulating the actin cytoskeleton.[5] Palladin, in contrast to myotilin and myopalladin, which are expressed only in striated muscle, is expressed ubiquitously in cells of mesenchymal origin.

Contents

[edit] Isoforms

In humans, it appears that seven different isoforms exist, some of which arise through alternative splicing.[6] 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.[3]

[edit] Function

Palladin's precise biological role is yet 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.[5]

[edit] Disease linkage

Recently, it has been demonstrated that palladin RNA is overexpressed in patients with pancreatic neoplasia, and that palladin is both overexpressed and mutated in an inherited form of pancreatic cancer.[7] 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.[8][9]

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,[10] 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.

It is interesting to note that 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).

[edit] Origin of name

Palladin was named after the Renaissance architect Andrea Palladio, reflecting its localization to architectural elements of the cell.

[edit] References

  1. ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (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. PMID 10231032. 
  2. ^ Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.154701. PMID 11230166. 
  3. ^ a b Parast MM, Otey CA (2000). "Characterization of palladin, a novel protein localized to stress fibers and cell adhesions". J. Cell Biol. 150 (3): 643–56. doi:10.1083/jcb.150.3.643. PMID 10931874. 
  4. ^ Mykkänen OM, Grönholm M, Rönty M, Lalowski M, Salmikangas P, Suila H, Carpén O (2001). "Characterization of human palladin, a microfilament-associated protein". Mol. Biol. Cell 12 (10): 3060–73. PMID 11598191. 
  5. ^ a b Otey CA, Rachlin A, Moza M, Arneman D, Carpen O (2005). "The palladin/myotilin/myopalladin family of actin-associated scaffolds". Int. Rev. Cytol. 246: 31–58. doi:10.1016/S0074-7696(05)46002-7. PMID 16164966. 
  6. ^ 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. PMID 16492705. 
  7. ^ Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA (2006). "Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism". PLoS Med. 3 (12): e516. doi:10.1371/journal.pmed.0030516. PMID 17194196. 
  8. ^ Slater E, Amrillaeva V, Fendrich V, Bartsch D, Earl J, Vitone LJ, Neoptolemos JP, Greenhalf W (2007). "Palladin mutation causes familial pancreatic cancer: absence in European families". PLoS Med. 4 (4): e164. doi:10.1371/journal.pmed.0040164. PMID 17455999. 
  9. ^ 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. PMID 17415588. 
  10. ^ Salaria SN, Illei P, Sharma R, Walter KM, Klein AP, Eshleman JR, Maitra A, Schulick R, Winter J, Ouellette MM, Goggins M, Hruban R (2007). "Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells". Cancer Biol. Ther. 6 (3): 324–8. PMID 17404500. 

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