Related Experiment Video
Updated: Apr 19, 2026
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
9.7K
RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy
Natalie Spang1, Anne Feldmann, Heike Huesmann
1a Institute for Pathobiochemistry ; University Medical Center of the Johannes Gutenberg University ; Mainz , Germany.
Autophagy
|December 16, 2014
Summary
RAB3GAP1 and RAB3GAP2 proteins regulate autophagy, a key cellular process for maintaining protein balance. These factors influence autophagosome formation and are vital for cellular proteostasis.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Macroautophagy is crucial for intracellular proteostasis, involving the transport of cellular components via autophagosomes to lysosomes.
- The precise membrane dynamics of autophagy remain incompletely understood and rely on complex trafficking pathways.
- RAB GTPase Activating Proteins (RABGAPs) are key regulators of cellular vesicle transport, with some TBC domain-containing RABGAPs linked to autophagy.
Purpose of the Study:
- To investigate the role of RAB3GAP1 and RAB3GAP2, components of the TBC domain-free RAB3GAP complex, in macroautophagy and proteostasis.
- To elucidate how RAB3GAP1/2 influence autophagosomal biogenesis and interact with other autophagy-related proteins.
- To determine the relationship between RAB3GAP1/2 and other known autophagy modulators like FEZ1 and FEZ2.
Main Methods:
- Utilized experiments in *C. elegans* and human primary fibroblasts.
- Assessed the impact of RAB3GAP1/2 on protein aggregation and autophagy under basal and induced conditions.
- Analyzed the colocalization of RAB3GAP1/2 with autophagy markers (Atg8 family) and their dependence on RAB3GAP1's GTPase-activating activity.
Main Results:
- RAB3GAP1/2 were found to influence protein aggregation and modulate autophagy, affecting both basal and rapamycin-induced conditions.
- RAB3GAP1/2 were shown to modulate autophagosomal biogenesis, correlating with ATG3 and ATG16L1 and affecting ATG5 punctate structures.
- RAB3GAP1/2 colocalized with Atg8 family members at lipid droplets, and their function was dependent on RAB3GAP1's GTPase-activating activity but not on RAB3.
- RAB3GAP1/2 were found to reciprocally regulate autophagy with FEZ1 and FEZ2.
Conclusions:
- RAB3GAP1 and RAB3GAP2 are identified as novel, conserved factors involved in the autophagy and proteostasis network.
- These proteins play a significant role in regulating autophagosome formation and cellular protein quality control.
- The findings highlight a new regulatory mechanism within the complex machinery of macroautophagy.
Keywords:
ATG, autophagy-relatedATG16L1ATG3BSA, bovine serum albuminBafi, bafilomycin A1C. elegans, Caenorhabditis elegansCALCOCO2, calcium binding and coiled-coil domain 2DAPI, 4’, 6-diamidino-2-phenylindoleDMSO, dimethyl sulfoxideDPH, 1, 6-diphenyl-1, 3, 5-hexatrieneFEZ, fasciculation and elongation protein zetaFEZ1FEZ2GABARAP, GABA(A) receptor-associated proteinGEF, guanine nucleotide exchange factorGFP, green fluorescent proteinMAP1LC3, microtubule-associated protein 1 light chain 3NBR1, neighbor of BRCA1 gene 1PBS, phosphate-buffered salinePE, phosphatidylethanolamineRAB3GAP1RAB3GAP2RABGAP, RAB GTPase activating proteinSQSTM1, sequestosome 1TBC domain, TRE2-BUB2-CDC16 domainautophagyeV, empty vectorlipid dropletsproteostasissiRNA, small interfering RNA
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
6.5K
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...
6.5K
01:25Rab Cascades
3.8K
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.
3.8K
01:14Rab Proteins
5.5K
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...
5.5K
03:03mTOR Signaling and Cancer Progression
5.1K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.1K
01:24Small GTPases - Ras and Rho
5.8K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
5.8K
01:07MAPK Signaling Cascades
9.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.5K