The adaptor protein-1 μ1B subunit expands the repertoire of basolateral sorting signal recognition in epithelial cells.
An outstanding question in protein sorting is why polarized epithelial cells express two isoforms of the μ1 subunit of the AP-1 clathrin adaptor complex: the ubiquitous μ1A and the epithelial-specific μ1B. Previous studies led to the notion that μ1A and μ1B mediate basolateral sorting predominantly from the trans-Golgi network (TGN) and recycling endosomes, respectively. Using improved analytical tools, however, we find that μ1A and μ1B largely colocalize with each other. They also colocalize to similar extents with TGN and recycling endosome markers, as well as with basolateral cargoes transiting biosynthetic and endocytic-recycling routes. Instead, the two isoforms differ in their signal-recognition specificity. In particular, μ1B preferentially binds a subset of signals from cargoes that are sorted basolaterally in a μ1B-dependent manner. We conclude that expression of distinct μ1 isoforms in epithelial cells expands the repertoire of signals recognized by AP-1 for sorting of a broader range of cargoes to the basolateral surface.
Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Xiaoli
X
Guo
Rafael
R
Mattera
Xuefeng
X
Ren
Yu
Y
Chen
Claudio
C
Retamal
Alfonso
A
González
Juan S
JS
Bonifacino
D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms; D021381:Protein Transport; D011973:Receptors, LDL / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
D033983:Adaptor Protein Complex mu Subunits; D015415:Biomarkers; D020033:Protein Isoforms; D011973:Receptors, LDL; D018808:Transcription Factor AP-1; D020823:ADP-Ribosylation Factor 1