Prickle (protein)

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]

prickle-like 1 (Drosophila)
Identifiers
SymbolPRICKLE1
NCBI gene144165
OMIM608500

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
SymbolPRICKLE2
NCBI gene166336
OMIM608501

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. Shimojo M, Hersh LB (December 2003). "REST/NRSF-interacting LIM domain protein, a putative nuclear translocation receptor". Molecular and Cellular Biology. 23 (24): 9025–31. doi:10.1128/mcb.23.24.9025-9031.2003. PMC 309669. PMID 14645515.
  2. Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, et al. (November 2008). "A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome". American Journal of Human Genetics. 83 (5): 572–81. doi:10.1016/j.ajhg.2008.10.003. PMC 2668041. PMID 18976727.
  3. Veeman MT, Slusarski DC, Kaykas A, Louie SH, Moon RT (April 2003). "Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements". Current Biology. 13 (8): 680–5. doi:10.1016/s0960-9822(03)00240-9. PMID 12699626.
  4. Tao H, Inoue K, Kiyonari H, Bassuk AG, Axelrod JD, Sasaki H, et al. (April 2012). "Nuclear localization of Prickle2 is required to establish cell polarity during early mouse embryogenesis". Developmental Biology. 364 (2): 138–48. doi:10.1016/j.ydbio.2012.01.025. PMC 3299875. PMID 22333836.
  5. Liu C, Lin C, Whitaker DT, Bakeri H, Bulgakov OV, Liu P, et al. (June 2013). "Prickle1 is expressed in distinct cell populations of the central nervous system and contributes to neuronal morphogenesis". Human Molecular Genetics. 22 (11): 2234–46. doi:10.1093/hmg/ddt075. PMC 3652420. PMID 23420014.
  6. Katoh M, Katoh M (February 2003). "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. doi:10.3892/ijmm.11.2.249. PMID 12525887.
  7. Tissir F, Goffinet AM (February 2006). "Expression of planar cell polarity genes during development of the mouse CNS". The European Journal of Neuroscience. 23 (3): 597–607. doi:10.1111/j.1460-9568.2006.04596.x. PMID 16487141.
  8. Mrkusich EM, Flanagan DJ, Whitington PM (October 2011). "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. doi:10.1016/j.ydbio.2011.07.032. PMID 21827745.
  9. Bastock R, Strutt H, Strutt D (July 2003). "Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning". Development. 130 (13): 3007–14. doi:10.1242/dev.00526. PMID 12756182.
  10. Jenny A, Reynolds-Kenneally J, Das G, Burnett M, Mlodzik M (July 2005). "Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding". Nature Cell Biology. 7 (7): 691–7. doi:10.1038/ncb1271. PMID 15937478.
  11. Gubb D, Green C, Huen D, Coulson D, Johnson G, Tree D, et al. (September 1999). "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. doi:10.1101/gad.13.17.2315. PMC 316995. PMID 10485852.
  12. Bassuk A. "Evaluating PRICKLE mutations in human epilepsy and animal models". Institute for Clinical and Translational Science at the University of Iowa. The University of Iowa. Archived from the original on 2015-04-15. Retrieved 2015-04-15.
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