Prickle is also known as REST/NRSF-interacting LIM domain protein, which is a putative nuclear translocation receptor. Prickle is part of the non-canonical Wnt signaling pathway that establishes planar cell polarity. A gain or loss of function of Prickle1 causes defects in the convergent extension movements of gastrulation. In epithelial cells, Prickle2 establishes and maintains cell apical/basal polarity. Prickle1 plays an important role in the development of the nervous system by regulating the movement of nerve cells. The first prickle

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

was identified in ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' as a

planar cell polarity Planar Cell Polarity (PCP) is the protein mediated signaling that coordinates the orientation of cells in a layer of epithelial tissue. In vertebrates, examples of mature PCP oriented tissue are the stereo-cilia bundles in the inner ear, motile cil ...

protein. Vertebrate prickle-1 was first found as a rat protein that binds to a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

, neuron-restrictive silencer factor (NRSF). It was then recognized that other vertebrates including mice and

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

s have two genes that are related to ''Drosophila'' prickle. Mouse prickle-2 was found to be expressed in mature

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

s of the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

along with mouse homologs of ''Drosophila'' planar polarity genes

flamingo Flamingos or flamingoes are a type of wading bird in the family Phoenicopteridae, which is the only extant family in the order Phoenicopteriformes. There are four flamingo species distributed throughout the Americas (including the Caribbea ...

and dischevelled. Prickle interacts with flamingo to regulate sensory axon advance at the transition between the peripheral nervous system and the central nervous system. Also, Prickle1 interacts with

RE1-silencing transcription factor RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the ''REST'' gene, and acts as a transcriptional repressor. REST is expressly involved in the repressi ...

(REST) by transporting REST out of the nucleus. REST turns off several critical genes in neurons by binding to particular regions of DNA in the nucleus. Prickle is recruited to the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

surface

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...

strabismus Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...

, another planar cell polarity protein. In the developing ''Drosophila'' wing, prickle becomes concentrated at the proximal side of cells. Prickle can compete with the ankyrin-repeat protein Diego for a binding site on Dishevelled. In ''Drosophila'', prickle is present inside cells in multiple forms due to alternative splicing of the prickle mRNA. The relative levels of the alternate forms may be regulated and involved in the normal control of planar cell polarity. Mutations in Prickle genes can cause epilepsy in humans by perturbing Prickle function. One mutation in Prickle1 gene can result in Prickle1-Related Progressive Myoclonus Epilepsy-Ataxia Syndrome. This mutation disrupts the interaction between prickle-like 1 and REST, which results in the inability to suppress REST. Gene knockdown of Prickle1 by shRNA or dominant-negative constructs results in decreased axonal and dendritic extension in neurons in the hippocampus. Prickle1 gene knockdown in neonatal retina causes defects in axon terminals of photoreceptors and in inner and outer segments.

References

External links

GeneReview/NCBI/NIH/UW entry on Progressive Myoclonus Epilepsy with Ataxia
{{DEFAULTSORT:Prickle (Protein) Signal transduction