Scaffolding protein GOPC regulates tight junction structure

Abstract

GOPC (FIG/PIST/CAL) is a PDZ-domain scaffolding protein that regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. In Madin-Darby Canine Kidney (MDCK) cells, we find that GOPC localizes to the Trans-Golgi Network (TGN), but not the cis or trans Golgi cisternae. There is also colocalization with the early endosome Rab GTPase Rab5 and a TGN/endosome marker Rab14, but not with Rab11, a marker of recycling endosomes. There is no localization of GOPC to the lateral membranes or tight junctions. We find that knockdown of GOPC in MDCK cells results in decreased transepithelial resistance and increased paracellular flux. This may be due to compromised trafficking of tight junction components from the TGN, as GOPC knockdown cells have decreased lateral labeling of the tight junction protein claudin-1 and decreased protein levels of claudin-2. GOPC may mediate trafficking of newly synthesized tight junction proteins from the TGN to the cell surface or recycling of these proteins from specialized endosomal compartments.

AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice

“…S2 ) as reported for Gopc KO mice 54 , 55 . Amongst these proteins, HRB has been directly linked to vesicle fusion 40 , GM130 is a cis -Golgi protein 56 , TMF1 is a golgin involved in Golgi morphology 57 , VPS54 is a component of the Golgi Associated Retrograde Protein (GARP) complex associated with tethering of endosome vesicles to the TGN 58 , GOPC and PICK1 have been shown to be involved in the budding and trafficking of vesicles from the TGN 42 , 59 , 60 , and MFSD14A may be important for protein or lipid glycosylation due to its homology to sugar transporters 49 . This suggests that the failure in the fusion of vesicles in these mutants takes place before the point in which proacrosomic vesicles are expected to fuse.…”

Tight Junction Proteins and the Biology of Hepatobiliary Disease

“…The TJ complex is known to be highly dynamic with continuous remodeling by clathrin-mediated endocytic recycling [37][38][39][40]. Recycled or newly produced TJ proteins are sorted in the Golgi-network and transported by specific trafficking proteins to the desired localizations [41,42]. On the other hand, several growth factors, cytokines, and signaling cascades induce and regulate localization and expression of TJ proteins, hereby affecting epithelial differentiation and barrier integrity [5,6].…”

Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST

“…PIST plays important roles in regulating the membrane targeting of transmembrane proteins [30–32]. Notably, PIST was shown to colocalize with the early endosome marker Rab5 and the TGN/endosome marker Rab14 [39]. Our data reveal that PCDH15-CD3 and CDH23 bind PIST via their C-terminal PBI and colocalize with PIST in the TGN, which might regulate the transportation of PCDH15 and CDH23 to the apical surface of hair cells.…”