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. 2020 Aug;65:112–121. doi: 10.1016/j.ceb.2020.05.009

Figure 2.

Figure 2

Retrograde trafficking in the polarized epithelium. Apicobasal polarity determinants: Note the polarized orientation of the Golgi facing the apical membrane. (a) The transmembrane protein Crumbs (Crbs) is an apicobasolateral polarity determinant that together with the Cdc42-Par6-aPKC protein complex controls the establishment and maintenance of apical domain identity. In Drosophila, Crumbs uses the retromer-dependent retrograde route for its apical transport/recycling, which is crucial for apical integrity. (b) Both the apical Crumbs and the lateral Scribble (SCRIB) scaffold protein are needed to stabilize the junction protein E-cadherin (E-cad) at the sub-apical membrane. When silenced, SCRIB induces an accumulation of E-cad within retromer positive structures before reaching the Golgi compartment, suggesting that in certain circumstances the retrograde machinery is involved in the polarized secretion of E-cad. (c) Apically located glycocalyx/gp135 is another key protein in the epithelium. In kidney epithelial cells, galectin-8 (Gal8) binds gp135 in a carbohydrate-dependent manner for post-Golgi delivery to the apical surface to regulate lumen formation. Whether Gal8 traffics from the apical membrane back to the Golgi for a new round of apical secretion of gp135 is an intriguing possibility. Polarized secretion: (d) Extracellular galectin-9 (Gal9) contributes to apicobasolateral polarity. Gal9 binds to the GSL Forssman antigen (FGL) and undergoes cycles of retrograde transport and polarized apical secretion. (e) Similarly to Gal9, other galectins including Gal3 and Gal4 are required for the maintenance of epithelial polarity by controlling the flotillin-dependent polarized secretion of apical proteins such as DPPIV and LPH. In contrast to Gal9, it has not yet been analyzed whether these galectins also undergo retrograde trafficking. (f) Wnt11 is specifically secreted to the apical surface in a process that involves Gal3. As part of its functional cycle, the Wnt receptor Wntless (Wls) undergoes retrograde transport to bind newly synthetized Wnt in the Golgi for subsequent polarized secretion. Whether Gal3 also contributes to the retrograde transport of Wls still needs to be investigated. (g) The GPI-anchored protein CD59 is first transported to the basolateral membrane before being transcytosed to the apical side in a clathrin-independent but dynamin and flotillin-dependent manner. A link between this transcytotic route and the retrograde pathway presents an interesting possibility.