在PTPδ中交替拼接的迷你exon B通过细胞类型特定的跨突触PTPδ-IL1RAP相互作用来调节激发性突触
Seoyeong Kim1,2, Jae Jin Shin2, Muwon Kang1,2
1Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, 34141, Korea.
Nature communications
|May 13, 2025
概括
蛋白氨酸酸酶三角酶 (PTPδ) 迷你外显子B (meB) 对于生存至关重要,并调节刺激性突触. 在小鼠中的PTPδ-meB突变导致异常行为和突触缺陷,由IL1RAP介导.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 由PTPRD编码的蛋白氨酸酸酶三角酶 (PTPδ) 与神经和神经发育障碍有关.
- PTPδ通过替代拼接的迷你外显子,meA和meB,与后突触粘附分子相互作用.
- 在体内PTPδ-meB的功能在很大程度上仍然未被描述.
研究的目的:
- 为了研究PTPδ-meB拼接变体的体内功能.
- 阐明PTPδ-meB在生存,突触功能和行为中的作用.
- 确定PTPδ-meB对激发性突触的影响背后的分子机制.
主要方法:
- 生产和分析同卵性PTPδ-meB突变小鼠 (Ptprd-meB-/-).
- 在异构卵性Ptprd-meB+/-小鼠中进行行为测试和电生理学记录.
- 后突触密度的蛋白质组分析和IL1RAP突变小鼠的研究.
主要成果:
- 同胞卵性Ptprd-meB-/-小鼠的早期出生后存活率降低.
- 异构卵性Ptprd-meB+/-雄性小鼠表现出行为异常,并且在牙状粒细胞 (DG-GCs) 中减少了激发性突触传播.
- 降低后突触IL1RAP水平与PTPδ-meB缺乏相关;IL1RAP突变小鼠显示激发性传播受损,而低IL1RAP的PTPδ-meB+/- 内神经元显示激发性传播增强.
结论:
- PTPδ-meB在早期生存,突触可塑性和行为方面发挥着至关重要的作用.
- PTPδ-meB以细胞类型特定的方式调节激发性突触.
- IL1RAP通路对于PTPδ-meB在调节突触传输中的功能至关重要.
更多相关视频
06:56Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
Published on: September 6, 2024
271
09:17Combining Optogenetics with Artificial microRNAs to Characterize the Effects of Gene Knockdown on Presynaptic Function within Intact Neuronal Circuits
Published on: March 14, 2018
10.1K
相关概念视频
Phosphoinositides and PIPs
7.3K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
7.3K
Alternative RNA Splicing
20.9K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
20.9K
IP3/DAG Signaling Pathway
11.7K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.7K
Postsynaptic Potential (PSP)
2.2K
Postsynaptic potential (PSP) refers to a change in the electrical potential of a neuron when neurotransmitters released by presynaptic neurons bind to postsynaptic receptors. This potential can either be excitatory, leading to depolarization and ultimately action potential generation, or inhibitory, leading to hyperpolarization and suppression of the postsynaptic neuron.
There are two types of receptors: ionotropic and metabotropic.
The ionotropic receptor is the membrane protein that has an...
There are two types of receptors: ionotropic and metabotropic.
The ionotropic receptor is the membrane protein that has an...
2.2K
GTPases and their Regulation
8.2K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.2K
Chromatin Structure Regulates pre-mRNA Processing
6.9K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
6.9K
