Mechanisms by Which SNX-BAR Subfamily Controls the Fate of SNXs' Cargo

Yaolin Long ¹ Yang Li ¹ Jin Xue ¹ Wanqing Geng ² Mingxia Ma ¹ Xiaohui Wang ¹ Li Wang ^1*

• ¹ Shanxi Medical University, Taiyuan, China
• ² Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

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.