Biology:Prickle (protein)
| prickle-like 1 (Drosophila) | |
|---|---|
| Identifiers | |
| Symbol | PRICKLE1 |
| NCBI gene | 144165 |
| OMIM | 608500 |
Prickle is also known as REST/NRSF-interacting LIM domain protein, which is a putative nuclear translocation receptor.[1] Prickle is part of the non-canonical Wnt signaling pathway that establishes planar cell polarity.[2] A gain or loss of function of Prickle1 causes defects in the convergent extension movements of gastrulation.[3] In epithelial cells, Prickle2 establishes and maintains cell apical/basal polarity.[4] Prickle1 plays an important role in the development of the nervous system by regulating the movement of nerve cells.[5]
The first prickle protein was identified in Drosophila as a planar cell polarity protein. Vertebrate prickle-1 was first found as a rat protein that binds to a transcription factor, neuron-restrictive silencer factor (NRSF). It was then recognized that other vertebrates including mice and humans have two genes that are related to Drosophila prickle.[6] Mouse prickle-2 was found to be expressed in mature neurons of the brain along with mouse homologs of Drosophila planar polarity genes flamingo and dischevelled.[7] Prickle interacts with flamingo to regulate sensory axon advance at the transition between the peripheral nervous system and the central nervous system.[8] Also, Prickle1 interacts with RE1-silencing transcription factor (REST) by transporting REST out of the nucleus.[1] REST turns off several critical genes in neurons by binding to particular regions of DNA in the nucleus.[1]
| prickle-like 2 (Drosophila) | |
|---|---|
| Identifiers | |
| Symbol | PRICKLE2 |
| NCBI gene | 166336 |
| OMIM | 608501 |
Prickle is recruited to the cell surface membrane by strabismus, another planar cell polarity protein.[9] In the developing Drosophila wing, prickle becomes concentrated at the proximal side of cells.[9] Prickle can compete with the ankyrin-repeat protein Diego for a binding site on Dishevelled.[10]
In Drosophila, prickle is present inside cells in multiple forms due to alternative splicing of the prickle mRNA.[11] The relative levels of the alternate forms may be regulated and involved in the normal control of planar cell polarity.[11]
Mutations in Prickle genes can cause epilepsy in humans by perturbing Prickle function.[12] One mutation in Prickle1 gene can result in Prickle1-Related Progressive Myoclonus Epilepsy-Ataxia Syndrome.[2] This mutation disrupts the interaction between prickle-like 1 and REST, which results in the inability to suppress REST.[2] Gene knockdown of Prickle1 by shRNA or dominant-negative constructs results in decreased axonal and dendritic extension in neurons in the hippocampus.[5] Prickle1 gene knockdown in neonatal retina causes defects in axon terminals of photoreceptors and in inner and outer segments.[5]
References
- ↑ 1.0 1.1 1.2 "REST/NRSF-interacting LIM domain protein, a putative nuclear translocation receptor". Molecular and Cellular Biology 23 (24): 9025–31. December 2003. doi:10.1128/mcb.23.24.9025-9031.2003. PMID 14645515.
- ↑ 2.0 2.1 2.2 "A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome". American Journal of Human Genetics 83 (5): 572–81. November 2008. doi:10.1016/j.ajhg.2008.10.003. PMID 18976727.
- ↑ "Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements". Current Biology 13 (8): 680–5. April 2003. doi:10.1016/s0960-9822(03)00240-9. PMID 12699626.
- ↑ "Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis". Developmental Biology 364 (2): 138–48. April 2012. doi:10.1016/j.ydbio.2012.01.025. PMID 22333836.
- ↑ 5.0 5.1 5.2 "Prickle1 is expressed in distinct cell populations of the central nervous system and contributes to neuronal morphogenesis". Human Molecular Genetics 22 (11): 2234–46. June 2013. doi:10.1093/hmg/ddt075. PMID 23420014.
- ↑ "Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle". International Journal of Molecular Medicine 11 (2): 249–56. February 2003. doi:10.3892/ijmm.11.2.249. PMID 12525887. http://www.spandidos-publications.com/ijmm/11/2/249.
- ↑ "Expression of planar cell polarity genes during development of the mouse CNS". The European Journal of Neuroscience 23 (3): 597–607. February 2006. doi:10.1111/j.1460-9568.2006.04596.x. PMID 16487141.
- ↑ "The core planar cell polarity gene prickle interacts with flamingo to promote sensory axon advance in the Drosophila embryo". Developmental Biology 358 (1): 224–30. October 2011. doi:10.1016/j.ydbio.2011.07.032. PMID 21827745.
- ↑ 9.0 9.1 "Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning". Development 130 (13): 3007–14. July 2003. doi:10.1242/dev.00526. PMID 12756182.
- ↑ "Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding". Nature Cell Biology 7 (7): 691–7. July 2005. doi:10.1038/ncb1271. PMID 15937478.
- ↑ 11.0 11.1 "The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs". Genes & Development 13 (17): 2315–27. September 1999. doi:10.1101/gad.13.17.2315. PMID 10485852.
- ↑ Bassuk, Alexander. "Evaluating PRICKLE mutations in human epilepsy and animal models". The University of Iowa. http://www.icts.uiowa.edu/content/evaluating-prickle-mutations-human-epilepsy-and-animal-models.
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