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]
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]