PMID- 16917501
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20230815
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 25
IP  - 17
DP  - 2006 Sep 6
TI  - Lysosome membrane lipid microdomains: novel regulators of chaperone-mediated 
      autophagy.
PG  - 3921-33
AB  - Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation 
      of soluble cytosolic proteins in lysosomes. The limiting step of this type of 
      autophagy is the binding of substrates to the lysosome-associated membrane 
      protein type 2A (LAMP-2A). In this work, we identify a dynamic 
      subcompartmentalization of LAMP-2A in the lysosomal membrane, which underlies the 
      molecular basis for the regulation of LAMP-2A function in CMA. A percentage of 
      LAMP-2A localizes in discrete lysosomal membrane regions during resting 
      conditions, but it exits these regions during CMA activation. Disruption of these 
      regions by cholesterol-depleting agents or expression of a mutant LAMP-2A 
      excluded from these regions enhances CMA activity, whereas loading of lysosomes 
      with cholesterol significantly reduces CMA. Organization of LAMP-2A into 
      multimeric complexes, required for translocation of substrates into lysosomes via 
      CMA, only occurs outside the lipid-enriched membrane microdomains, whereas the 
      LAMP-2A located within these regions is susceptible to proteolytic cleavage and 
      degradation. Our results support that changes in the dynamic distribution of 
      LAMP-2A into and out of discrete microdomains of the lysosomal membrane 
      contribute to regulate CMA.
FAU - Kaushik, Susmita
AU  - Kaushik S
AD  - Department of Anatomy and Structural Biology, Marion Bessin Liver Research 
      Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
FAU - Massey, Ashish C
AU  - Massey AC
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
LA  - eng
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - AG25355/AG/NIA NIH HHS/United States
GR  - AG-NS-0163/AG/NIA 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
DEP - 20060817
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Molecular Chaperones)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
CIN - Autophagy. 2007 Jul-Aug;3(4):387-9. PMID: 17438364
MH  - Amino Acid Sequence
MH  - Animals
MH  - Autophagy/*physiology
MH  - Cholesterol/metabolism
MH  - Intracellular Membranes/*metabolism/ultrastructure
MH  - Lysosomal-Associated Membrane Protein 2/genetics/*metabolism
MH  - Lysosomes/*metabolism/ultrastructure
MH  - Male
MH  - Membrane Microdomains/*metabolism/ultrastructure
MH  - Mice
MH  - Microscopy, Immunoelectron
MH  - Molecular Chaperones/*physiology
MH  - Molecular Sequence Data
MH  - Mutation
MH  - NIH 3T3 Cells
MH  - Protein Transport
MH  - Rats
MH  - Rats, Wistar
PMC - PMC1560360
EDAT- 2006/08/19 09:00
MHDA- 2006/10/25 09:00
PMCR- 2007/09/06
CRDT- 2006/08/19 09:00
PHST- 2006/02/16 00:00 [received]
PHST- 2006/07/25 00:00 [accepted]
PHST- 2006/08/19 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/08/19 09:00 [entrez]
PHST- 2007/09/06 00:00 [pmc-release]
AID - 7601283 [pii]
AID - 10.1038/sj.emboj.7601283 [doi]
PST - ppublish
SO  - EMBO J. 2006 Sep 6;25(17):3921-33. doi: 10.1038/sj.emboj.7601283. Epub 2006 Aug 
      17.