Microautophagy of cytosolic proteins by late endosomes.
Autophagy delivers cytosolic components to lysosomes for their degradation. The delivery of autophagic cargo to late endosomes for complete or partial degradation has also been described. In this report we present evidence that distinct autophagic mechanisms control cytosolic protein delivery to late endosomes and identify a microautophagy-like process that delivers soluble cytosolic proteins to the vesicles of late endosomes/multivesicular bodies (MVBs). This microautophagy-like process has selectivity and is distinct from chaperone-mediated autophagy that occurs in lysosomes. Endosomal microautophagy occurs during MVB formation, relying on the ESCRT I and III systems for formation of the vesicles in which the cytosolic cargo is internalized. Protein cargo selection is mediated by the chaperone hsc70 and requires the cationic domain of hsc70 for electrostatic interactions with the endosomal membrane. Therefore, we propose that endosomal microautophagy shares molecular components with both the endocytic and autophagic pathways.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ranjit
R
Sahu
Susmita
S
Kaushik
Cristina C
CC
Clement
Elvira S
ES
Cannizzo
Brian
B
Scharf
Antonia
A
Follenzi
Ilaria
I
Potolicchio
Edward
E
Nieves
Ana Maria
AM
Cuervo
Laura
L
Santambrogio
D000818:Animals; D001343:Autophagy; D003600:Cytosol / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D057146:Multivesicular Bodies / Q000378:metabolism / Q000648:ultrastructure; D041681:NIH 3T3 Cells; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D050883:HSC70 Heat-Shock Proteins; D052119:Lysosomal-Associated Membrane Protein 2; D014157:Transcription Factors; D000099177:Tsg101 Protein
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