Related Experiment Video
Updated: May 17, 2026
09:42
High-Resolution 3D Imaging of Rabies Virus Infection in Solvent-Cleared Brain Tissue
Published on: April 30, 2019
AP-3 and Rabip4' coordinately regulate spatial distribution of lysosomes
Viorica Ivan1, Emma Martinez-Sanchez, Livia E Sima
1Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
Plos One
|November 13, 2012
Summary
Silencing RUFY1 gene products promotes plasma membrane protrusions and lysosome clustering. The adaptor protein complex AP-3 and rabip4
Area of Science:
- Cell Biology
- Molecular Biology
- Cellular Dynamics
Background:
- Rabip4 and rabip4' are RUN and FYVE domain proteins encoded by RUFY1, differing in an N-terminal extension.
- Their C terminus binds rab5 and rab4, but their precise functions remain unclear.
Purpose of the Study:
- To investigate the function of rabip4' in cellular processes.
- To identify proteins interacting with rabip4' and elucidate their collaborative roles.
Main Methods:
- RUFY1 gene silencing to observe cellular changes.
- Interactor screening to identify rabip4' binding partners.
- Colocalization studies of rabip4' with identified interactors.
Main Results:
- Silencing RUFY1 induced plasma membrane protrusions with clustered lysosomes at their tips.
- The adaptor protein complex AP-3 was identified as a rabip4' interactor, binding via its β3 subunit hinge region to rabip4's FYVE domain.
- AP-3 knockdown exacerbated lysosome accumulation in plasma membrane protrusions, with peripheral lysosomes located within the cortical actin network.
Conclusions:
- Rabip4' and AP-3 play a novel role in regulating lysosome positioning.
- These proteins function within an interorganellar pathway to control lysosome localization.
Related Concept Videos
01:25Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
01:22Lysosomal Hydrolases
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
01:14Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
01:31Lysosomes
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
00:58Recycling Endosomes and Transcytosis
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
01:28The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...