Regulation of postendocytic trafficking of the epidermal growth factor receptor through endosomal retention.
J Biol Chem
; 269(17): 12865-73, 1994 Apr 29.
Article
in En
| MEDLINE
| ID: mdl-8175702
ABSTRACT
Little is known about the regulation of EGF receptor (EGF-R) trafficking following endocytosis. We investigated this by using a series of EGF-R with altered cytoplasmic tails and comparing their ability to undergo recycling and lysosomal targeting in both the occupied and empty state. We found that 2-3% of empty EGF-R are internalized each minute, but rapidly recycle (t1/2 approximately 5 min). This constitutive internalization and recycling of empty receptors was independent of cytoplasmic receptor sequences. Occupied EGF-R, in contrast, displayed a much slower rate of recycling (t1/2 between 10-23 min) due to retention within recycling endosomes. Endosomal retention of different EGF-R correlated with lysosomal targeting of EGF. Intrinsic receptor tyrosine kinase activity had no discernible effect on postendocytic trafficking of EGF. Although sequences within the cytoplasmic tail of the EGF-R appear to be required for occupancy-dependent endosomal retention, they are distinct from those required for ligand-induced endocytosis. Our studies indicate that intracellular trafficking of the EGF-R is regulated by endosomal components that preferentially recognize occupied receptors. Down-regulation of the EGF-R thus involves two distinct regulatory processes one at the level of internalization and one at the level of recycling.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organelles
/
Endocytosis
/
ErbB Receptors
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
1994
Document type:
Article