RGD Reference Report - The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. - Rat Genome Database

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The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane.

Authors: Bandyopadhyay, U  Kaushik, S  Varticovski, L  Cuervo, AM 
Citation: Bandyopadhyay U, etal., Mol Cell Biol. 2008 Sep;28(18):5747-63. doi: 10.1128/MCB.02070-07. Epub 2008 Jul 21.
RGD ID: 10412301
Pubmed: (View Article at PubMed) PMID:18644871
DOI: Full-text: DOI:10.1128/MCB.02070-07

Chaperone-mediated autophagy (CMA) is a selective type of autophagy by which specific cytosolic proteins are sent to lysosomes for degradation. Substrate proteins bind to the lysosomal membrane through the lysosome-associated membrane protein type 2A (LAMP-2A), one of the three splice variants of the lamp2 gene, and this binding is limiting for their degradation via CMA. However, the mechanisms of substrate binding and uptake remain unknown. We report here that LAMP-2A organizes at the lysosomal membrane into protein complexes of different sizes. The assembly and disassembly of these complexes are a very dynamic process directly related to CMA activity. Substrate proteins only bind to monomeric LAMP-2A, while the efficient translocation of substrates requires the formation of a particular high-molecular-weight LAMP-2A complex. The two major chaperones related to CMA, hsc70 and hsp90, play critical roles in the functional dynamics of the LAMP-2A complexes at the lysosomal membrane. Thus, we have identified a novel function for hsc70 in the disassembly of LAMP-2A from these complexes, whereas the presence of lysosome-associated hsp90 is essential to preserve the stability of LAMP-2A at the lysosomal membrane.


Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)
Hsp90ab1  (heat shock protein 90 alpha family class B member 1)
Hspa8  (heat shock protein family A (Hsp70) member 8)
Lamp2  (lysosomal-associated membrane protein 2)

Objects referenced in this article
Gene LOC100362895 heat shock protein 1, alpha-like Rattus norvegicus

Additional Information