chaperone-mediated autophagy translocation complex disassembly
Definition
Target type: biologicalprocess
The disaggregation of a chaperone-mediated autophagy translocation complex into its constituent components. [GO_REF:0000079, GOC:pad, GOC:PARL, GOC:TermGenie, PMID:18644871]
Chaperone-mediated autophagy (CMA) is a selective form of autophagy that relies on the recognition of specific target proteins by chaperones, particularly the heat shock cognate protein 70 (HSC70). The translocation complex, responsible for delivering cargo to the lysosome, is formed by the interaction of the target protein, HSC70, the lysosome-associated membrane protein 2A (LAMP-2A), and the CMA receptor, located on the lysosomal membrane. The disassembly of this complex is crucial for the successful completion of CMA, allowing the cargo to be delivered into the lysosome for degradation.
The disassembly of the CMA translocation complex is a multi-step process that involves the following:
1. **Cargo recognition and binding:** The target protein, bearing a KFERQ-like motif, is recognized by HSC70. This recognition event triggers the recruitment of the CMA receptor, LAMP-2A, to the complex.
2. **Translocation to the lysosome:** The HSC70-target protein complex, with LAMP-2A bound, translocates to the lysosome. This step involves the movement of the complex through the cytoplasm and the fusion of the lysosomal membrane with the complex.
3. **Disassembly and cargo delivery:** Upon reaching the lysosome, the complex undergoes disassembly. This involves the release of the target protein from HSC70 and the removal of LAMP-2A from the receptor. The target protein is then delivered into the lysosomal lumen for degradation, while HSC70 and LAMP-2A are recycled back to the cytoplasm.
The exact mechanisms underlying the disassembly of the CMA translocation complex are still being investigated. However, it is believed that the process involves the following factors:
* **Lysosomal proteases:** Lysosomal proteases, such as cathepsins, are thought to play a role in degrading the target protein and releasing it from HSC70.
* **Lysosomal pH:** The acidic environment of the lysosome may promote the dissociation of the complex.
* **ATP hydrolysis:** HSC70 is an ATPase, and ATP hydrolysis may provide energy for the disassembly process.
* **Other lysosomal proteins:** Several other lysosomal proteins, such as LAMP-1 and LAMP-2B, may be involved in regulating the disassembly of the CMA translocation complex.
The disassembly of the CMA translocation complex is a critical step in the CMA pathway, ensuring the efficient delivery of cargo to the lysosome for degradation. The process involves complex interactions between multiple proteins and is influenced by a variety of factors, including the lysosomal environment and the activity of specific enzymes.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Heat shock cognate 71 kDa protein | A heat shock cognate 71 kDa protein that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| adenosine diphosphate | Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. | adenosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | fundamental metabolite; human metabolite |
| tubercidin | tubercidin : An N-glycosylpyrrolopyrimidine that is adenosine in which the in the 5-membered ring that is not attached to the ribose moiety is replaced by a carbon. Tubercidin is produced in the culture broth of Streptomyces tubericidus. Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids. | antibiotic antifungal agent; N-glycosylpyrrolopyrimidine; ribonucleoside | antimetabolite; antineoplastic agent; bacterial metabolite |
| toyocamycin | toyocamycin : An N-glycosylpyrrolopyrimidine that is tubercidin in which the hydrogen at position 5 of the pyrrolopyrimidine moiety has been replaced by a cyano group. Toyocamycin: 4-Amino-5-cyano-7-(D-ribofuranosyl)-7H- pyrrolo(2,3-d)pyrimidine. Antibiotic antimetabolite isolated from Streptomyces toyocaensis cultures. It is an analog of adenosine, blocks RNA synthesis and ribosome function, and is used mainly as a tool in biochemistry. | antibiotic antifungal agent; N-glycosylpyrrolopyrimidine; nitrile; ribonucleoside | antimetabolite; antineoplastic agent; apoptosis inducer; bacterial metabolite |
| nsc 65346 | sangivamycin : A nucleoside analogue that is adenosine in which the nitrogen at position 7 is replaced by a carbamoyl-substituted carbon. It is a potent inhibitor of protein kinase C. sangivamycin: RN given refers to parent cpd | nucleoside analogue | protein kinase inhibitor |
| adenosine | quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| 8-aminoadenosine | |||
| 5'-deoxyadenosine | 5'-deoxyadenosine : A 5'-deoxyribonucleoside compound having adenosine as the nucleobase. 5'-deoxyadenosine: main heading DEOXYADENOSINE refers to the 3' cpd | 5'-deoxyribonucleoside; adenosines | Escherichia coli metabolite; human metabolite; mouse metabolite |
| ver 155008 | VER 155008: structure in first source | purine nucleoside | |
| nms-e973 | NMS-E973: structure in first source |