regulation of endosomal vesicle fusion
Definition
Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of endosomal vesicle fusion. [GO_REF:0000058, GOC:bc, GOC:PARL, GOC:TermGenie, PMID:26911690]
Regulation of endosomal vesicle fusion is a complex and tightly controlled process essential for various cellular functions, including nutrient uptake, signal transduction, and the degradation of internalized molecules. Endosomes, membrane-bound compartments within cells, act as sorting hubs for internalized materials. They receive cargo from the plasma membrane and transport it to various destinations, including lysosomes for degradation, the Golgi apparatus for recycling, or back to the cell surface. The fusion of endosomes with other compartments is mediated by a precise interplay of proteins, lipids, and signaling pathways.
The process begins with the recognition and tethering of endosomes, mediated by proteins like Rab GTPases and tethering factors. Rab GTPases act as molecular switches, cycling between active GTP-bound and inactive GDP-bound states. Specific Rab GTPases are associated with different endosomal subdomains, facilitating their sorting and fusion with target compartments. Tethering factors, on the other hand, bridge the gap between Rab-coated endosomes and their fusion partners.
Once tethered, endosomes undergo a series of conformational changes to facilitate membrane fusion. This is driven by SNARE proteins, a family of transmembrane proteins that assemble into complexes to bring the membranes of two compartments together. SNARE proteins are categorized as v-SNAREs (on vesicle membranes) and t-SNAREs (on target membranes). Specific SNARE pairings are required for distinct fusion events.
The assembly of SNARE complexes triggers the formation of a trans-SNARE complex, spanning the two membranes. This complex pulls the membranes together, ultimately leading to fusion. The fusion process requires a precise balance of regulatory mechanisms to ensure efficient and specific delivery of cargo.
Regulation of endosomal vesicle fusion is influenced by various factors, including:
* **Small GTPases:** Besides Rab GTPases, other small GTPases like Arf and Rho GTPases are involved in regulating membrane trafficking and fusion events.
* **Lipid composition:** The lipid composition of endosomal membranes, including phosphoinositides, is crucial for regulating fusion events.
* **Phosphatases and kinases:** These enzymes modify proteins involved in membrane trafficking, influencing their activity and localization.
* **Ubiquitination:** Ubiquitination of proteins can regulate their sorting and targeting to specific endosomal compartments.
* **Signaling pathways:** Various signaling pathways, like those activated by growth factors or cytokines, can influence endosomal fusion by altering the activity of regulatory proteins.
Defects in the regulation of endosomal vesicle fusion can lead to various cellular dysfunctions and diseases, including neurodegenerative disorders, immune deficiencies, and cancer. Understanding the intricacies of this process is crucial for developing therapeutic strategies for treating these diseases.'
"
Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Sphingosine kinase 1 | A sphingosine kinase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NYA1] | Homo sapiens (human) |
Compounds (10)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| fingolimod hydrochloride | fingolimod hydrochloride : The hydrochloride salt of 2-amino-2-[2-(4-octylphenyl) ethyl]-1,3-propanediol (fingolimod). Fingolimod Hydrochloride: A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS. | hydrochloride | immunosuppressive agent; prodrug; sphingosine-1-phosphate receptor agonist |
| 4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol | substituted aniline | ||
| safingol | safingol: RN given refers to the (R-(R*,S*))-isomer | amino alcohol | |
| sphingosine | 2-aminooctadec-4-ene-1,3-diol : A 2-aminooctadecene-1,3-diol having its double bond at position 4. sphing-4-enine : A sphingenine in which the C=C double bond is located at the 4-position. sphingenine : A 2-aminooctadecene-1,3-diol having (2S,3R)-configuration. sphingoid : Sphinganine, its homologs and stereoisomers, and the hydroxy and unsaturated derivatives of these compounds. | sphing-4-enine | human metabolite; mouse metabolite |
| n,n-dimethylsphingenine | N,N-dimethylsphingosine : A sphingoid that is sphingosine in which the two amino hydrogens are replaced by methyl groups. N,N-dimethylsphingosine: a sphingosine kinase inhibitor | aminodiol; sphingoid; tertiary amino compound | EC 2.7.1.91 (sphingosine kinase) inhibitor; metabolite |
| es-285 | 1-deoxysphinganine : A bioactive sphingoid, sphinganine, in which the terminal hydroxy group has been replaced by a hydrogen. spisulosine: from marine organism, Spisula polynyma; structure in first source | amino alcohol; sphingoid | antineoplastic agent |
| 3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide | organochlorine compound | ||
| bml 258 | |||
| pf-543 | PF-543: Sphingosine Kinase 1 Selective Inhibitor; structure in first source | sulfonamide | |
| rome | (2R)-2-amino-2-(methoxymethyl)-4-(4-octylphenyl)butan-1-ol : A 2-amino-2-(methoxymethyl)-4-(4-octylphenyl)butan-1-ol that has R-configuration. It is a sphingosine kinase-2 inhibitor. Rome: The capital city of Italy. | 2-amino-2-(methoxymethyl)-4-(4-octylphenyl)butan-1-ol | EC 2.7.1.91 (sphingosine kinase) inhibitor |