PI(4)P-Dependent Recruitment of Clathrin Adaptors to the Trans-Golgi Network

Simple item page
dc.contributor.advisorYin, Helen L.en
dc.creatorWang, Jingen
dc.date.accessioned2010-07-12T17:39:12Z
dc.date.available2010-07-12T17:39:12Z
dc.date.issued2005-04-29
dc.description.abstractThe Trans Golgi Network (TGN) is the cell's central sorting station, and the complex trafficking patterns are organized by many types of trafficking adaptors. These include the heterotetrameric adaptor protein complexes (APs) and the monomeric Golgi-localized, gamma-ear containing, Arf-binding proteins (GGAs). The fundamental question of how these adaptors are recruited to TGN membrane remains unclear. Previous studies have shown that adaptor recruitment to the TGN is absolutely dependent on the small GTPase ADP ribosylation factor 1 (Arf1), but paradoxically, Arf1 has a broader intracellular distribution than these adaptors. We found that the Golgi is particularly enriched in phosphatidylinositol 4 phosphate [PI(4)P] and that the clathrin adaptor AP-1 binds PI(4)P directly, suggesting that PI(4)P binding may specify the TGN-specific recruitment in conjunction with Arf1. My studies showed that another monomeric clathrin adaptor GGA also binds PI(4)P and Arf1 independently. The C-terminal "triple helix bundle" of the GGA GAT domain is a polyfunctional module that interacts with multiple partners including PI(4)P and ubiquitin, and ubiquitin may provide a recognition signal for GGAs to control protein sorting. We found that PI(4)P increases wild type GAT binding to ubiquitin-conjugated agarose beads, but has no effect on a mutant GAT that does not bind PI(4)P. Therefore, PI(4)P may be an allosteric regulator of GGAs which enhances ubiquitin binding to GGAs. Based on these results, we conclude: (1) PI(4)P defines the TGN organelle identity by recruiting TGN-targeted adaptors; (2) TGN-enriched adaptors are recruited to the Golgi by binding to both PI(4)P and Arf1, and neither alone is sufficient; (3) PI(4)P acts as a scaffold, and may also be an allosteric regulator for GGAs that modulates GGA function with other ligands. We propose that the integration of combinatorial inputs from PI(4)P, Arf1 and ubiquitin may coordinately specify clathrin adaptor TGN recruitment through multiple low-affinity interactions.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc60593182
dc.identifier.urihttps://hdl.handle.net/2152.5/340
dc.language.isoenen
dc.subjecttrans-Golgi Networken
dc.subjectClathrinen
dc.subjectTranscription Factor AP-1en
dc.subjectVesicular Transport Proteinsen
dc.subjectADP-Ribosylation Factor 1en
dc.subjectPhosphatidylinositol Phosphatesen
dc.subjectUbiquitinsen
dc.subjectAdaptor Proteins, Vesicular Transporten
dc.titlePI(4)P-Dependent Recruitment of Clathrin Adaptors to the Trans-Golgi Networken
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2005-04-29
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineIntegrative Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
wangjing.pdf
Size:
3.11 MB
Format:
Adobe Portable Document Format
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
942 B
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

UT Southwestern Graduate School of Biomedical Sciences