Palladin is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''PALLD''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Palladin is a component of
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
-containing microfilaments that control cell shape,
adhesion
Adhesion is the tendency of dissimilar particles or interface (matter), surfaces to cling to one another. (Cohesion (chemistry), Cohesion refers to the tendency of similar or identical particles and surfaces to cling to one another.)
The ...
, and contraction.
Discovery
Palladin was characterised independently by two research groups, first in the lab of Carol Otey (in 2000)
and then in the lab of Olli Carpén (in 2001).
It is a part of the myotilin-myopalladin-palladin family and may play an important role in modulating the
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
.
Palladin, in contrast to
myotilin and
myopalladin, which are expressed only in
striated muscle
Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. Under the microscope, sarcomeres are visible along muscle fibers, giving a striated appearance to the tissue. The two types of striated muscle a ...
, is expressed ubiquitously in cells of
mesenchymal
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...
origin.
Palladin was named after the Italian Renaissance architect
Andrea Palladio
Andrea Palladio ( , ; ; 30 November 1508 – 19 August 1580) was an Italian Renaissance architect active in the Venetian Republic. Palladio, influenced by Roman and Greek architecture, primarily Vitruvius, is widely considered to be on ...
, reflecting its localization to architectural elements of the cell.
Isoforms
In humans, it appears that seven different isoforms exist, some of which arise through
alternative splicing
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
.
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.
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.
Disease linkage
Recently, it has been demonstrated that palladin
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
is overexpressed in patients with
pancreatic neoplasia
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, and that palladin is both overexpressed and mutated in an inherited form of
pancreatic cancer
Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...
.
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.
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,
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
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. C ...
).
Interactions
PALLD has been shown to
interact with
EZR.
References
Further reading
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External links
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{{PDB Gallery, geneid=23022