PMID- 18644871
OWN - NLM
STAT- MEDLINE
DCOM- 20080929
LR  - 20240415
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 28
IP  - 18
DP  - 2008 Sep
TI  - The chaperone-mediated autophagy receptor organizes in dynamic protein complexes 
      at the lysosomal membrane.
PG  - 5747-63
LID - 10.1128/MCB.02070-07 [doi]
AB  - 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.
FAU - Bandyopadhyay, Urmi
AU  - Bandyopadhyay U
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
FAU - Kaushik, Susmita
AU  - Kaushik S
FAU - Varticovski, Lyuba
AU  - Varticovski L
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
LA  - eng
GR  - P01 DK041918/DK/NIDDK NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - AG25355/AG/NIA NIH HHS/United States
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - DK041918/DK/NIDDK NIH HHS/United States
GR  - R21 AG025355/AG/NIA NIH HHS/United States
GR  - AG021904/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080721
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - Animals
MH  - Autophagy/*physiology
MH  - Cell Line
MH  - HSC70 Heat-Shock Proteins/genetics/*metabolism
MH  - HSP90 Heat-Shock Proteins/genetics/*metabolism
MH  - Humans
MH  - Intracellular Membranes/chemistry/*metabolism
MH  - Lysosomal-Associated Membrane Protein 2/chemistry/genetics/*metabolism
MH  - *Lysosomes/metabolism/ultrastructure
MH  - Male
MH  - Mice
MH  - Molecular Weight
MH  - Multiprotein Complexes/chemistry/*metabolism
MH  - Protein Isoforms/chemistry/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
PMC - PMC2546938
EDAT- 2008/07/23 09:00
MHDA- 2008/09/30 09:00
PMCR- 2009/03/01
CRDT- 2008/07/23 09:00
PHST- 2008/07/23 09:00 [pubmed]
PHST- 2008/09/30 09:00 [medline]
PHST- 2008/07/23 09:00 [entrez]
PHST- 2009/03/01 00:00 [pmc-release]
AID - MCB.02070-07 [pii]
AID - 2070-07 [pii]
AID - 10.1128/MCB.02070-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2008 Sep;28(18):5747-63. doi: 10.1128/MCB.02070-07. Epub 2008 Jul 
      21.