Palladin

Palladin is a protein that in humans is encoded by the PALLD gene.[5][6][7][8] Palladin is a component of actin-containing microfilaments that control cell shape, adhesion, and contraction.[8]

PALLD
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPALLD, CGI-151, CGI151, MYN, PNCA1, SIH002, palladin, cytoskeletal associated protein
External IDsOMIM: 608092 MGI: 1919583 HomoloGene: 75052 GeneCards: PALLD
Orthologs
SpeciesHumanMouse
Entrez

23022

72333

Ensembl

ENSG00000129116

ENSMUSG00000058056

UniProt

Q8WX93

Q9ET54

RefSeq (mRNA)

NM_001081390
NM_001293772
NM_001293773
NM_001293774

RefSeq (protein)

NP_001074859
NP_001280701
NP_001280702
NP_001280703

Location (UCSC)Chr 4: 168.5 – 168.93 MbChr 8: 61.96 – 62.36 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Discovery

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 the actin cytoskeleton.[10] 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 Italian Renaissance architect Andrea Palladio, reflecting its localization to architectural elements of the cell.[6]

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.[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]

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.[10]

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.[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 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).

Interactions

PALLD has been shown to interact with EZR.[9]

References
  1. GRCh38: Ensembl release 89: ENSG00000129116 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000058056 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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. PMID 10231032.
  6. Parast MM, Otey CA (Sep 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. PMC 2175193. PMID 10931874.
  7. 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.GR1547R. PMC 311072. PMID 11230166.
  8. "Entrez Gene: PALLD palladin, cytoskeletal associated protein". nih.gov.
  9. 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. doi:10.1091/mbc.12.10.3060. PMC 60155. PMID 11598191.
  10. Otey 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. Vol. 246. pp. 31–58. doi:10.1016/S0074-7696(05)46002-7. ISBN 9780123646507. PMID 16164966.
  11. 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.
  12. 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. PMC 1751121. PMID 17194196.
  13. 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. PMC 1855695. PMID 17455999.
  14. 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. S2CID 2445261.
  15. 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. doi:10.4161/cbt.6.3.3904. PMC 3144721. PMID 17404500.

Further reading
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