Related Experiment Video
Updated: Jul 7, 2026
08:52
Assaying Circuit Specific Regulation of Adult Hippocampal Neural Precursor Cells
Published on: July 24, 2019
A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis
Quan-Hong Ma1, Toshitaka Futagawa, Wu-Lin Yang
1Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.
Nature Cell Biology
|February 19, 2008
Summary
The study identifies TAG1 as a functional ligand of amyloid precursor protein (APP). This TAG1-APP interaction negatively regulates neurogenesis via Fe65, impacting neural stem cell development.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Amyloid precursor protein (APP) intracellular domain (AICD) signaling is crucial in cellular processes.
- Fe65 is known to bind AICD, but its functional ligand has remained uncharacterized.
- Gamma-secretase-dependent cleavage releases AICD.
Purpose of the Study:
- To identify the functional ligand of APP involved in AICD-dependent signaling.
- To elucidate the role of this ligand in neurogenesis and its interaction with APP and Fe65.
Main Methods:
- Investigated the interaction between TAG1 and APP.
- Assessed the effect of TAG1 on AICD release and Fe65-dependent activity.
- Utilized knockout mouse models (TAG1-/-, APP-/-, TAG1-/-;APP-/-, Fe65-/-) to study neurogenesis.
- Examined colocalization of TAG1, APP, and Fe65 in neural stem cell niches.
Main Results:
- TAG1 was identified as a functional ligand of APP.
- Extracellular TAG1 interaction with APP increased AICD release and Fe65-dependent activity in a gamma-secretase-dependent manner.
- TAG1, APP, and Fe65 colocalized in the fetal ventricular zone neural stem cell niche.
- TAG1 deficiency or APP deficiency led to enhanced neurogenesis, which was reversed by TAG1 or AICD in TAG1-/- mice.
- TAG1 reduced normal neurogenesis in Fe65+/+ mice, and this effect was abolished in Fe65-/- mice.
Conclusions:
- TAG1 acts as a functional ligand for APP, initiating a signaling pathway.
- The TAG1-APP-Fe65 pathway negatively modulates neurogenesis in neural precursor cells.
- This pathway is critical for regulating the proliferation of neural stem cells during development.
Related Concept Videos
01:15Neurogenesis and Regeneration of Nervous Tissue
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...