Prickle (protein)

Last updated
prickle-like 1 (Drosophila)
Identifiers
SymbolPRICKLE1
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
SymbolPRICKLE2
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]

Related Research Articles

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

Peripherin

Peripherin is a type III intermediate filament protein expressed mainly in neurons of the peripheral nervous system. It is also found in neurons of the central nervous system that have projections toward peripheral structures, such as spinal motor neurons. Its size, structure, and sequence/location of protein motifs is similar to other type III intermediate filament proteins such as desmin, vimentin and glial fibrillary acidic protein. Like these proteins, peripherin can self-assemble to form homopolymeric filamentous networks, but it can also heteropolymerize with neurofilaments in several neuronal types. This protein in humans is encoded by the PRPH gene. Peripherin is thought to play a role in neurite elongation during development and axonal regeneration after injury, but its exact function is unknown. It is also associated with some of the major neuropathologies that characterize amyotropic lateral sclerosis (ALS), but despite extensive research into how neurofilaments and peripherin contribute to ALS, their role in this disease is still unidentified.

L1 (protein) Mammalian protein found in Homo sapiens

L1, also known as L1CAM, is a transmembrane protein member of the L1 protein family, encoded by the L1CAM gene. This protein, of 200-220 kDa, is a neuronal cell adhesion molecule with a strong implication in cell migration, adhesion, neurite outgrowth, myelination and neuronal differentiation. It also plays a key role in treatment-resistant cancers due to its function. It was first identified in 1984 by M. Schachner who found the protein in post-mitotic mice neurons.

Silencer (genetics)

In genetics, a silencer is a DNA sequence capable of binding transcription regulation factors, called repressors. DNA contains genes and provides the template to produce messenger RNA (mRNA). That mRNA is then translated into proteins. When a repressor protein binds to the silencer region of DNA, RNA polymerase is prevented from transcribing the DNA sequence into RNA. With transcription blocked, the translation of RNA into proteins is impossible. Thus, silencers prevent genes from being expressed as proteins.

Flamingo is a member of the adhesion-GPCR family of proteins. Flamingo has sequence homology to cadherins and G protein-coupled receptors (GPCR). Flamingo was originally identified as a Drosophila protein involved in planar cell polarity. Mammals have three flamingo homologs, CELSR1, CELSR2, CELSR3. In mice all three have distinct expression patterns in the brain.

Strabismus was originally identified as a Drosophila protein involved in planar cell polarity. Flies with mutated strabismus genes have altered development of ommatidia in their eyes. Vertebrates have two Strabismus-related proteins, VANGL1 and VANGL2.

FZD3 Protein-coding gene in the species Homo sapiens

Frizzled-3 is a protein that in humans is encoded by the FZD3 gene.

DVL1

Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.

DVL2

Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.

DVL3

Segment polarity protein dishevelled homolog DVL-3 is a protein that in humans is encoded by the DVL3 gene.

EMX2 Protein-coding gene in the species Homo sapiens

Homeobox protein Emx2 is a protein that in humans is encoded by the EMX2 gene.

SLIT1

Slit homolog 1 protein is a protein that in humans is encoded by the SLIT1 gene.

Dentatorubral–pallidoluysian atrophy Congenital disorder of nervous system

Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration caused by an expansion of a CAG repeat encoding a polyglutamine tract in the atrophin-1 protein. It is also known as Haw River Syndrome and Naito–Oyanagi disease. Although this condition was perhaps first described by Smith et al. in 1958, and several sporadic cases have been reported from Western countries, this disorder seems to be very rare except in Japan.

Dishevelled

Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs. There are vertebrate homologs in zebrafish, Xenopus (Xdsh), mice and humans. Dsh relays complex Wnt signals in tissues and cells, in normal and abnormal contexts. It is thought to interact with the novel protein, SPATS1, when regulating the Wnt Signalling pathway.

Slit is a family of secreted extracellular matrix proteins which play an important signalling role in the neural development of most bilaterians. While lower animal species, including insects and nematode worms, possess a single Slit gene, humans, mice and other vertebrates possess three Slit homologs: Slit1, Slit2 and Slit3. Human Slits have been shown to be involved in certain pathological conditions, such as cancer and inflammation.

Collapsin response mediator protein family or CRMP family consists of five intracellular phosphoproteins of similar molecular size and high (50–70%) amino acid sequence identity. CRMPs are predominantly expressed in the nervous system during development and play important roles in axon formation from neurites and in growth cone guidance and collapse through their interactions with microtubules. Cleaved forms of CRMPs have also been linked to neuron degeneration after trauma induced injury.

KCTD7

Potassium channel tetramerisation domain containing 7 is a protein in humans that is encoded by the KCTD7 gene. Alternative splicing results in multiple transcript variants.

Evx1 is a mammalian gene located downstream of the HoxA cluster, which encodes for a homeobox transcription factor. Evx1 is a homolog of even-skipped (eve), which is a pair-rule gene that regulates body segmentation in Drosophila. The expression of Evx1 is developmentally regulated, displaying a biphasic expression pattern with peak expression in the primitive streak during gastrulation and in interneurons during neural development. Evx1 has been shown to regulate anterior-posterior patterning during gastrulation by acting as a downstream effector of the Wnt and BMP signalling pathways. It is also a critical regulator of interneuron identity.

PRICKLE1

Prickle planar cell polarity protein 1 is a protein that in humans is encoded by the PRICKLE1 gene.

Prickle planar cell polarity protein 2

Prickle planar cell polarity protein 2 is a protein that in humans is encoded by the PRICKLE2 gene.

References

  1. 1 2 3 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. 1 2 3 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. 1 2 3 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. S2CID   2729733.
  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. 1 2 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. S2CID   26142041.
  11. 1 2 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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