What does this research mean for the field?

The Parkinson's disease-linked D620N mutation in VPS35 causes subtle overall changes to its protein interactome but selectively reduces interactions with key partners such as the WASH complex, TBC1D5, and VPS29 in the mammalian brain. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

What question did this study set out to answer?

To determine how the Parkinson's disease-linked D620N mutation in VPS35 alters its protein interactome and impairs retromer complex function in mammalian cells and brain tissue.

September 3, 2026Neurobiology of DiseaseOpen Access

Parkinson's disease-linked D620N mutation selectively alters the brain-specific protein interactome of VPS35

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Authors

EWErin T. Williams MFMaxwell Frye XCXi Chen

Discussion

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Overview

Proteomic study reveals selective disruption of retromer interactions in cellular and rodent models, suggesting targeted rather than global disruption underlies VPS35-linked Parkinson's disease.

Key Points

To determine how the Parkinson's disease-linked D620N mutation in VPS35 alters its protein interactome and impairs retromer complex function in mammalian cells and brain tissue.
Conducted interactome proteomics using tandem affinity purification and chemical crosslinking co-immunoprecipitation in HEK-293T cells expressing wild-type or D620N VPS35.
Profiled the brain interactome via viral-mediated overexpression of human VPS35 in adult rat brains and endogenous VPS35 knockin mouse models using hemi-brain and striatal tissues.
Expression of D620N VPS35 led to a marked reduction in binding affinity with components of the endosomal WASH complex in human cell culture.
Endogenous knockin mouse models demonstrated a selective decrease in VPS35 binding to partner proteins TBC1D5 and VPS29 across both hemi-brain and striatum, despite high overall interactome and proteome preservation.

Cite This Study

Williams et al. (2026) studied this question.

synapsesocial.com/papers/6a993487636c6408cfa7c447 https://doi.org/10.1016/j.nbd.2026.107593

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September 3, 2026Neurobiology of DiseaseOpen Access

Parkinson's disease-linked D620N mutation selectively alters the brain-specific protein interactome of VPS35

View Full Paper

Ask AI

Bookmark

Authors

EWErin T. Williams MFMaxwell Frye XCXi Chen

Discussion

Member takes

Overview

Proteomic study reveals selective disruption of retromer interactions in cellular and rodent models, suggesting targeted rather than global disruption underlies VPS35-linked Parkinson's disease.

Key Points

To determine how the Parkinson's disease-linked D620N mutation in VPS35 alters its protein interactome and impairs retromer complex function in mammalian cells and brain tissue.
Conducted interactome proteomics using tandem affinity purification and chemical crosslinking co-immunoprecipitation in HEK-293T cells expressing wild-type or D620N VPS35.
Profiled the brain interactome via viral-mediated overexpression of human VPS35 in adult rat brains and endogenous VPS35 knockin mouse models using hemi-brain and striatal tissues.
Expression of D620N VPS35 led to a marked reduction in binding affinity with components of the endosomal WASH complex in human cell culture.
Endogenous knockin mouse models demonstrated a selective decrease in VPS35 binding to partner proteins TBC1D5 and VPS29 across both hemi-brain and striatum, despite high overall interactome and proteome preservation.

Cite This Study

Williams et al. (2026) studied this question.

synapsesocial.com/papers/6a993487636c6408cfa7c447 https://doi.org/10.1016/j.nbd.2026.107593

View Full Paper

Ask AI

Bookmark