Mechanisms by which SNX-BAR subfamily controls the fate of SNXs’ cargo

TL;DR

This review explains how the SNX-BAR subfamily helps control where proteins go inside cells and how it might be linked to diseases like heart and brain disorders.

Contribution

The paper provides a comprehensive overview of the SNX-BAR subfamily's role in intracellular cargo sorting and its potential disease implications.

Findings

SNX-BAR subfamily uses a BAR domain to induce membrane curvature and manage cargo sorting.

The subfamily connects endo-lysosomal, autophagolysosomal, and ubiquitin-proteasome pathways for protein homeostasis.

Dysfunction in SNX-BAR may contribute to cardiovascular and neurodegenerative diseases.

Abstract

The SNX-BAR subfamily is a component of the sorting nexins (SNXs) superfamily. Distinct from other SNXs, which feature a PX domain for phosphoinositide binding, the SNX-BAR subfamily includes a BAR domain that induces membrane curvature. Members of the SNX-BAR subfamily work together to recognize and select specific cargo, regulate receptor signaling, and manage cargo sorting both with and without the involvement of sorting complexes. They play a crucial role in maintaining cellular homeostasis by directing intracellular cargo to appropriate locations through endo-lysosomal, autophagolysosomal, and ubiquitin-proteasome pathways. This subfamily thus links various protein homeostasis pathways. This review examines the established and hypothesized functions of the SNX-BAR subfamily, its role in intracellular protein sorting and stability, and explores the potential involvement of subfamily dysfunction in the pathophysiology of cardiovascular and neurodegenerative diseases.

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