prickle planar cell polarity protein 1
The PRICKLE1 gene provides instructions for making a protein called prickle homolog 1. The function of this protein is unclear, although it appears to play an important role in the development of the nervous system. Prickle homolog 1 is likely part of a chemical signaling pathway known as noncanonical Wnt signaling. During development before birth, noncanonical Wnt signaling helps to determine the position of various components within cells (cell polarity). This pathway also regulates the movement of nerve cells (neurons) in the developing nervous system.
Studies suggest that prickle homolog 1 interacts with other proteins, including RE1-silencing transcription factor (REST). The REST protein regulates several critical genes in neurons by turning off (suppressing) their activity. To regulate these genes, REST must enter the nucleus and attach (bind) to particular regions of DNA. Researchers believe that prickle homolog 1 controls REST by transporting it out of the nucleus, which prevents it from binding to DNA and suppressing gene activity. It remains unclear how the interaction between prickle homolog 1 and REST contributes to the normal development of the nervous system.
At least three mutations in the PRICKLE1 gene have been identified in people with PRICKLE1-related progressive myoclonus epilepsy with ataxia. Each mutation changes a single protein building block (amino acid) in the prickle homolog 1 protein. One of the known mutations appears to disrupt the interaction between prickle homolog 1 and REST, blocking the transport of REST out of the nucleus. As a result, REST may inappropriately suppress certain genes in the developing nervous system. It is unclear how mutations in the PRICKLE1 gene lead to movement problems, seizures, and the other features of PRICKLE1-related progressive myoclonus epilepsy with ataxia.
- prickle homolog 1
- prickle-like 1
- REST (RE-1 silencing transcription factor)/NRSF (neuron-restrictive silencer factor)-interacting LIM domain protein
- REST/NRSF-interacting LIM domain protein