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First published online May 4, 2004
doi: 10.1242/10.1242/jcs.01217


Journal of Cell Science 117, 2183-2192 (2004)
Published by The Company of Biologists 2004
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The subapical compartment: a traffic center in membrane polarity development

Dick Hoekstra*, Donatienne Tyteca and Sven C. D. van IJzendoorn

Department of Membrane Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands



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Fig. 1. Membrane trafficking pathways in polarized epithelial cells. Macromolecules, internalized either from the basolateral (1) or apical (10) surface, are delivered to basolateral early endosomes (BEEs) and apical early endosomes (AEEs), respectively. From here, molecules can recycle to the plasma membrane domain of origin (2, 11), or are directed in the degradative, late endosomal (LE)/lysosomal (LYS) pathway (5, 6). Alternatively, basolaterally (3) and apically (12) derived molecules are sorted into a recycling route and meet in a compartment, referred to as the common endosome (CE), subapical compartment (SAC), or apical recycling endosome (ARE). From here, polarized recycling can occur to the basolateral (4) or apical (8) surface. Apical surface targeting can occur directly from the CE/SAC (8), or following a relay from the CE/SAC via the ARE (9) (for details, see text and Fig. 3). From the CE/SAC, proteins can also reach the lysosomes (7). In the biosynthetic pathway, molecules are sorted directly to the basolateral (13) or apical (14) surface. In the latter, some proteins might travel via CE/SAC, prior to their delivery to the apical surface domain (15). AJ, adherens junctions; TJ, tight junctions.

 


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Fig. 2. Visualization of the apical endomembrane system, following internalization of a fluorescent marker by apical endocytosis. (A) Overlap of a marker for apical endocytosis (Texas-Red-labeled dextran), endolyn-78 (green) and Rab11 (blue). Note the overlap of endolyn-78 and Rab11 (cyan) and the overlap of dextran and Rab11 (magenta). Colocalization of all three probes (white) is restricted to the pericanalicular region. Small compartments (<300 nm) are distinguishable close to the apical membrane that contain both endolyn-78 and Rab11, probably reflecting their colocalization in the SAC, as endolyn-78 accumulates in the SAC prior to its delivery to lysosomes. Note that Rab11 is thought to be particularly enriched in the distal part of the SAC or ARE. (B) Overlap of a marker for apical endocytosis with endolyn-78 and basolateral-to-apical transcytosing polymeric IgA receptor (pIgAR). Note the overlap of dextran and endolyn-78 (yellow), of endolyn-78 and pIgAR (cyan), some of which overlaps dextran (white), and of dextran with pIgR-dIgA (magenta). Bars, 5 µm. The apical endocytic pathway (i.e. the route from the AEE to the SAC to lysosomes taken by dextran) intersects the transcytotic route taken by pIgR-dIgA in a small (<300 nm) endolyn-positive SAC. (C-F) Electron micrographs of liver infused retrogradely with HRP for various time intervals. HRP initially localizes to 60-100 nm tubulovesicular structures close to the apical surface (C, 5 minutes). After 10 minutes, multivesicular bodies (MVBs; D) and cup-shaped vesicles (150-200 nm; E) became labeled with HRP, prior to delivery to the lysosomes (F; 15 minutes). Bar, 500 nm. For further details, see text and Rahner et al. (Rahner et al., 2000Go).

 


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Fig. 3. Organization of the endosomal recycling system in polarized epithelial cells. The SAC/CE is accessible both to apical and basolateral early-endosome-derived transport pathways. Its most distal part is defined as the ARE and is considered an integral subcompartment whose stability is dependent on microtubules. This subcompartment is involved in relaying molecules to the apical surface as the final step in the overall basolateral-to-apical transcytotic pathway. For further details, see text. Colored arrows depict apical or basolateral transport routes. AEE, apical early endosome; AJ, adherens junctions; ARE, apical recycling endosome; BEE, basolateral early endosome; CE, common endosome; dIgA, dimeric immunoglobulin A/pIg-receptor complex; GlcCer, glucosylceramide; SAC, subapical compartment; SM, sphingomyelin; TfR, transferrin receptor; TJ, tight junctions.

 





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