The polarized epithelia-specific mu 1B-adaptin complements mu 1A-deficiency in fibroblasts.
The heterotetrameric AP-1A adaptor complex of clathrin-coated vesicles is ubiquitously expressed. The mu 1-adaptin subunit of the complex exists as the ubiquitous mu 1A and the polarized epithelia-specific mu 1B, which are 80% identical. In polarized epithelia, mu 1B is incorporated into the AP-1B complex, which is required for basolateral plasma membrane sorting of the low-density lipoprotein receptor. Binding of AP-1B to subdomains of the trans-Golgi network (TGN) appears to be part of the mechanism by which protein sorting is mediated. We expressed mu 1B in mu 1A-deficient fibroblasts to test for mu 1B function in non-polarized cells. AP-1B complexes were formed and bound to the TGN and to endosomes. Moreover, AP-1B restored the AP-1A-dependent sorting of mannose 6-phosphate receptors between endosomes and the TGN. This demonstrates that mu 1A and mu 1B do have overlapping sorting functions and indicates that AP-1A and AP-1B mediate protein sorting along parallel pathways between the TGN and endosomes in polarized epithelia.
Eskelinen
Eeva-Liisa
EL
School of Life Sciences, Center for High Resolution Imaging and Processing, University of Dundee, Dundee DD1 5EH, UK.
Meyer
Christoph
C
Ohno
Hiroshi
H
von Figura
Kurt
K
Schu
Peter
P
D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism*; D000818:Animals; D002402:Cathepsin D; D016764:Cell Polarity; D002966:Clathrin / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism* / Q000648:ultrastructure
D033983:Adaptor Protein Complex mu Subunits; D002966:Clathrin; D017527:Receptor, IGF Type 2; D001619:beta-N-Acetylhexosaminidases; D002402:Cathepsin D