Tau expression and phosphorylation in enteroendocrine cells
Guillaume Chapelet1, Nora Béguin1, Blandine Castellano2
1Nantes Université, INSERM, CHU Nantes, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France.
Frontiers in Neuroscience
|June 19, 2023
Summary
This study found that tau protein is present and phosphorylated in human gut enteroendocrine cells (EEC). Short-chain fatty acids like propionate and butyrate can reduce tau phosphorylation at Thr205 in these cells.
Area of Science:
- Neuroscience
- Gastroenterology
- Cell Biology
Background:
- The gut-brain axis is implicated in Parkinson's disease (PD) pathogenesis.
- Enteroendocrine cells (EEC) in the gut lumen are increasingly recognized for their role in PD.
- Alpha-synuclein and tau proteins are key players in neurodegeneration, with potential interplay.
Purpose of the Study:
- To investigate the presence, isoform profile, and phosphorylation state of tau protein in human EEC.
- To explore the impact of short-chain fatty acids (SCFAs) on tau phosphorylation in EEC.
Main Methods:
- Immunohistochemistry on human colon specimens using anti-tau and EEC marker antibodies.
- Western blot and RT-PCR analysis of tau expression and isoforms in EEC lines (GLUTag, NCI-H716).
- Lambda phosphatase treatment to assess tau phosphorylation and SCFA treatment to evaluate its effect on tau phosphorylation at Thr205.
Main Results:
- Tau protein is expressed and phosphorylated in EEC from adult human colon.
- EEC lines predominantly express two tau isoforms, phosphorylated under basal conditions.
- Propionate and butyrate treatment decreased tau phosphorylation at Thr205 in GLUTag cells.
Conclusions:
- This is the first study to characterize tau in human EEC and EEC lines.
- Findings suggest a role for tau in EEC function and potential relevance to tauopathies and synucleinopathies.
- Provides a foundation for further research into tau's function in EEC and its link to neurodegenerative diseases.
Related Concept Videos
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
01:22Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
01:22PI3K/mTOR/AKT Signaling Pathway
3.7K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.7K
01:58Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
01:25cAMP-dependent Protein Kinase Pathways
6.4K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K
01:20The JAK-STAT Signaling Pathway
9.0K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.0K