Mar 31, 2020

Retromer forms low order oligomers on supported lipid bilayers

BioRxiv : the Preprint Server for Biology
Joseph PickrellChristopher G Burd

Abstract

Retromer is a protein sorting device that orchestrates the selection and export of integral membrane proteins from the endosome via retrograde and plasma membrane recycling pathways. Long standing hypotheses regarding the Retromer sorting mechanism posit that oligomeric interactions between Retromer and associated accessory factors on the endosome membrane drives clustering of Retromer-bound integral membrane cargo prior to its packaging into a nascent transport carrier. To test this hypothesis, we examined interactions between the components of the SNX3-Retromer sorting pathway using quantitative single particle fluorescence microscopy of a reconstituted system comprising a supported bilayer, Retromer, a model cargo protein, the accessory proteins SNX3, RAB7, and the Retromer-binding segment of the WASHC2C subunit of the WASH complex. The predominant species of membrane associated Retromer are low order: monomers (~18%), dimers (~35%), trimers (~24%) and tetramers (~24%). Unexpectedly, neither cargo nor accessory factors promote Retromer oligomerization on a supported bilayer. The results indicate that Retromer has an intrinsic propensity to form low order oligomers and that neither membrane association nor accessory factors p...Continue Reading

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Mentioned in this Paper

Diabetes Mellitus, Non-Insulin-Dependent
Mendelian Randomization Analysis
Human Genetics
Body Mass Index Procedure
High Density Lipoproteins
Pharmaceutical Preparations
Body Mass Index
Heart Diseases
Lipoprotein (a)
Population Group

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