summary: Researchers have discovered a surprising new function for a protein in the brain, RPT6, that could revolutionize the understanding and treatment of memory disorders.
RPT6 has long been known for its role in the hippocampal proteasome complex, but it has now been shown to bind DNA and regulate gene expression during memory formation.
This dual function of RPT6 provides new insights into the complex process of memory formation and has potential for therapeutic intervention against conditions such as Alzheimer’s disease and PTSD.
Important facts:
- RPT6 has been identified to have a dual role. RPT6 is part of the proteasome complex and also controls gene expression during memory formation.
- The discovery provides new insights into memory processes and could lead to better treatments for memory disorders.
- Research by Virginia Tech could have a major impact on future research on Alzheimer’s disease, dementia, PTSD, and other memory-related disorders.
sauce: Virginia Tech
Virginia Tech researchers have discovered a new function for a common protein in the brain. This development sheds new light on the mysteries of the mind and has promising implications for the treatment of memory loss and post-traumatic stress disorder.
This protein normally acts as part of a larger protein complex called the proteasome, which performs necessary housekeeping within the brain’s hippocampus by destroying other proteins.
But researchers in the College of Agriculture and Life Sciences’ Department of Animal Sciences recently noticed that the protein, called RPT6, operates in a previously undetected way.
“We discovered that RPT6 can exert a completely different function by binding to DNA and increasing the expression of other genes and proteins during memory formation,” said Tim Jarome, associate professor of neurobiology. Ta. “This indicates that RPT6 plays a unique dual role in memory formation, both inside and outside the proteasome complex.”
This discovery was made this month. neuroscience journala new avenue to explore how RPT6 functions in the brain and how it can be manipulated to improve memory and reduce memory disorders such as Alzheimer’s disease and post-traumatic stress disorder (PTSD). will be held.
The project was led by Kayla Farrell, a research scientist with a Ph.D. She graduated from the Faculty of Animal Science in December. Farrell previously led research to identify proteins that could lead to better treatments for women with PTSD.
Gene expression is essential for memory formation. Helps build the neural networks necessary for memory formation and consolidation. Researchers do not yet understand why RPT6 has this dual function or how it helps control which cells are recruited to form memories.
“There has to be something else working with it to regulate gene expression,” Jarome says. “We’re currently trying to understand how that’s done.”
Ultimately, this discovery will inform ongoing research in Jarome’s lab focused on understanding and treating memory disorders such as Alzheimer’s disease, dementia, and PTSD.
“This discovery takes us in some new directions in understanding the complexity of the brain and how we learn and store memories,” Jarome said. “We hope this will help point us in a new direction for understanding how gene expression is regulated during memory. In the long term, this could help control and improve memory, or This could lead to potential therapeutic targets for the treatment of maladaptive memory.”
Main findings
- Two features of RPT6: RPT6 is a protein present in all cells, and its role within the proteasome complex has long been known. This study revealed that RPT6 can also bind to DNA and regulate gene expression during memory formation, exhibiting a unique dual function.
- Effects of memory operations: Understanding the dual role of RPT6 provides insight into the complex process of memory formation. This knowledge could pave the way for targeted therapeutic interventions to enhance memory or reduce negative memories associated with conditions such as PTSD.
- Significance for future research: This study is an important step in understanding the complexity of the brain and the regulation of gene expression during memory formation. The researchers hope that further investigation of the mechanism of RPT6 will provide new directions for understanding memory at the molecular level.
About this memory research news
author: Margaret Ashburn
sauce: Virginia Tech
contact: Margaret Ashburn – Virginia Tech
image: Image credited to Neuroscience News
Original research: Closed access.
“Phosphorylation of RPT6 controls its ability to bind DNA and regulate gene expression in the hippocampus of male rats during memory formation” by Tim Jarome et al. neuroscience journal
abstract
Phosphorylation of RPT6 controls its ability to bind DNA and regulate gene expression in the hippocampus of male rats during memory formation
Memory formation requires coordinated control of gene expression, protein synthesis, and protein degradation via the ubiquitin-proteasome system (UPS). The 26S proteasome, a catalytic component of the UPS, contains a 20S catalytic core surrounded by two 19S regulatory caps, and phosphorylation of serine 120 of the 19S cap regulatory subunit RPT6 (pRPT6-S120) is activity-dependent. It is thought to be widely involved in the control of sex increase. in proteasome activity.
Recently, RPT6 was also shown to act outside the proteasome and play a transcription factor-like role in the hippocampus during memory formation. However, little is known about the proteasome-independent functions of “free” RPT6 in the brain or during memory formation and whether S120 phosphorylation is required for this transcriptional regulatory function.
Here we use RNA sequencing and novel genetic approaches as well as biochemical, molecular, and behavioral assays to show that pRPT6-S120 functions independently of the proteasome to bind to DNA and during memory formation. We tested the hypothesis that it regulates gene expression. RNA sequencing after siRNA-mediated knockdown of free RPT6 revealed 46 gene targets in the dorsal hippocampus of male rats after fear conditioning, and RPT6 was involved in transcriptional activation and repression.
By artificially positioning RPT6 to target genes via CRISPR-dCas9, we discovered that only RPT6 DNA binding may be important for changes in gene expression after learning.
Furthermore, CRISPR-dCas13-mediated conversion of S120 on RPT6 to glycine reveals that phosphorylation of S120 is required for RPT6 to bind to DNA and properly regulate transcription during memory formation. became.
Together we uncover a novel function of RPT6 phosphorylation in controlling gene transcription during memory formation.