Related Experiment Video
Updated: Aug 6, 2025
09:45
An Oligonucleotide-based Tandem RNA Isolation Procedure to Recover Eukaryotic mRNA-Protein Complexes
Published on: August 18, 2018
11.1K
The P4-ATPase Drs2 interacts with and stabilizes the multisubunit tethering complex TRAPPIII in yeast
Irene Pazos1, Marta Puig-Tintó1, Laura Betancur1
1Department of Medicine and Life Sciences (MELIS), Pompeu Fabra University (UPF), Barcelona, Spain.
EMBO Reports
|March 17, 2023
Summary
P4-ATPases, lipid flippases, regulate Multisubunit Tethering Complexes (MTCs) involved in vesicle transport. This interaction is crucial for selective autophagy and vesicle delivery, independent of the flippases
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- Multisubunit Tethering Complexes (MTCs) mediate vesicle tethering to acceptor membranes.
- Regulatory mechanisms of MTCs by other cellular components are not fully understood.
- P4-ATPases are a family of lipid flippases with known roles in membrane trafficking.
Purpose of the Study:
- To systematically investigate the protein interactome regulating MTCs.
- To explore the interaction between P4-ATPases and MTCs in Golgi-mediated transport.
- To elucidate the mechanism and biological significance of P4-ATPase-MTC interplay in Atg9 vesicle transport during selective autophagy.
Main Methods:
- Systematic interactome analysis.
- Biochemical assays using P4-ATPase Drs2 as a model.
- Investigating the role of the I(S/R)TTK motif in P4-ATPase-MTC interactions.
Main Results:
- Identified interactions between P4-ATPases and MTCs (e.g., TRAPPIII) involved in anterograde and retrograde Golgi transport.
- Demonstrated that binding of TRAPPIII subunit Trs85 to Drs2 stabilizes TRAPPIII on Atg9-loaded membranes.
- Showed this interaction is essential for Atg9 vesicle delivery in selective autophagy, independent of canonical P4-ATPase lipid-flipping activity.
Conclusions:
- P4-ATPases play a regulatory role in MTC function beyond their lipid-flipping activity.
- The interaction between P4-ATPases and MTCs, mediated by the I(S/R)TTK motif, is crucial for selective autophagy.
- Suggests a broader role for P4-ATPases in regulating membrane tethering complexes.
More Related Videos
Related Concept Videos
01:20Cotranslational Protein Translocation
7.4K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.4K
01:28Protein Translocation Machinery on the ER Membrane
4.7K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.7K
01:45Tail-anchoring of Proteins in the ER Membrane
3.1K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K
01:34ATP Driven Pumps II: P-type Pumps
5.0K
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
5.0K
01:30ATP Driven Pumps III: V-type Pumps
3.8K
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
3.8K
01:18ATP Synthase: Structure
12.7K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
12.7K