Sorting nexins: role in the regulation of blood pressure

Huang, Juan; Tiu, Andrew; José, Pedro A.; Yang, Jian

doi:10.1111/febs.16305

Cited by 6 publications

(2 citation statements)

References 186 publications

(284 reference statements)

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“…The structures of some coat proteins in vesicle formation, such as COPII, COPI, and Clathrin, have been determined to explore how they induce membrane remodeling . As a key component of coat proteins, Sorting nexins (SNX) proteins act a crucial role in endosomal pathways, and dysfunction of SNX proteins is associated with neurodegenerative, cardiovascular, and cancerous diseases. − How SNX proteins bend the membrane to generate the vesicles in trafficking has attracted great interest.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Membrane Curvature Induced by SNX1: Insights from Molecular Dynamics Simulations

Liao,

Si,

Kai

et al. 2024

J. Phys. Chem. B

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SNX proteins have been found to induce membrane remodeling to facilitate the generation of transport carriers in endosomal pathways. However, the molecular mechanism of membrane bending and the role of lipids in the bending process remain elusive. Here, we conducted coarse-grained molecular dynamics simulations to investigate the role of the three structural modules (PX, BAR, and AH) of SNX1 and the PI3P lipids in membrane deformation. We observed that the presence of all three domains is essential for SNX1 to achieve a stable membrane deformation. BAR is capable of remodeling the membrane through the charged residues on its concave surface, but it requires PX and AH to establish stable membrane binding. AH penetrates into the lipid membrane, thereby promoting the induction of membrane curvature; however, it is inadequate on its own to maintain membrane bending. PI3P lipids are also indispensable for membrane remodeling, as they play a dominant role in the interactions of lipids with the BAR domain. Our results enhance the comprehension of the molecular mechanism underlying SNX1-induced membrane curvature and help future studies of curvature-inducing proteins.

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Section: Introductionmentioning

confidence: 99%

Mechanism of Membrane Curvature Induced by SNX1: Insights from Molecular Dynamics Simulations

Liao,

Si,

Kai

et al. 2024

J. Phys. Chem. B

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“…Conserved throughout eukaryotes, defects in the function of these proteins are linked with various pathologies, including Alzheimer’s disease (AD) 3 , where they are associated with trafficking and processing 1, 4–6 , Down’s syndrome (DS) 7 , cancer 8 , schizophrenia, hypertension 9 , thyroid disorders, and epilepsy 7 . The pathological implications of sorting nexin is an emerging area of extensive investigation 7 .…”

Section: Introductionmentioning

confidence: 99%

Insights into cargo sorting by SNX32 in neuronal and non-neuronal cells: physiological implications in neurite outgrowth

Datta

Sugatha

Priya

et al. 2022

Preprint

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Sorting nexins (SNX) are a family of proteins containing the Phox homology domain, which shows a preferential endo-membrane association and regulates cargo sorting processes. Even with the vast amount of information unveiled systematically, the underlying mechanism of sorting remains elusive. Here, we established that SNX32, a SNX-BAR (Bin/Amphiphysin/Rvs) sub-family member, is associated with SNX4 via its BAR domain. We identified A226, Q259, E256, R366 of SNX32, and Y258, S448 of SNX4 at the interface of these two SNX proteins that are important for maintaining the association. Via its PX domain, SNX32 interacts with the Transferrin receptor (TfR) and Cation Independent Mannose-6-Phosphate Receptor (CIMPR). We showed that the conserved F131 in its PX domain is important in stabilising the above interactions. Silencing of SNX32 led to a defect in intracellular trafficking of TfR and CIMPR, which could be rescued by overexpressing shRNA-resistant snx32. We also showed that both individual domains play an essential role in trafficking. Our results indicate that SNX4, SNX32 and Rab11 may participate in a common pathway regulating transferrin trafficking; however, the existence of an independent pathway for Rab11 and SNX32 could not be completely ruled out. Further, we established that the PX domain of SNX32 could bind to PI(3)P and PI(4)P, suggesting a possible explanation for its sub-cellular localization. Taken together, our study showed that SNX32 mediate the trafficking of specific cargo molecules along distinct pathway via its PX domain-directed binding to phosphoinositides and its BAR domain-mediated association with other SNX family members. Further, using SILAC-based differential proteomics of the wild type and the mutant SNX32, impaired in cargo binding, we identified Basigin (BSG), an immunoglobulin super family member, as a potential interactor of SNX32 in SH-SY-5Y cells. We then demonstrated that SNX32 binds to BSG through its PX domain and facilitates its trafficking to the cell surface. In Neuro-Glial cell lines, the silencing of SNX32 led to defects in neuronal differentiation. Moreover, abrogation in lactate transport in the SNX32 depleted cells led us to propose that the SNX may contribute to maintaining the neuro-glial coordination via its role in BSG trafficking and the associated Monocarboxylate transporter activity.

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Sorting nexins as a promising therapeutic target for cardiovascular disorders: An updated overview

Yarmohammadi

Hayes

Karimi

2022

Experimental Cell Research

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Sorting nexins: role in the regulation of blood pressure

Cited by 6 publications

References 186 publications

Mechanism of Membrane Curvature Induced by SNX1: Insights from Molecular Dynamics Simulations

Mechanism of Membrane Curvature Induced by SNX1: Insights from Molecular Dynamics Simulations

Insights into cargo sorting by SNX32 in neuronal and non-neuronal cells: physiological implications in neurite outgrowth

Sorting nexins as a promising therapeutic target for cardiovascular disorders: An updated overview

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