Molecular mechanisms of Sorting nexin-9 in membrane triggered actin polymerisation
type: CreativeWork
description: Sorting nexin-9 (SNX9) is a SH3-PX-BAR domain-containing adaptor protein, func- tionally implicated in regulating actin polymerisation in clathrin mediated endocy- tosis and filopodia formation. Alterations in SNX9 expression correlate with several stages of breast cancer metastasis, and poor patient survival in colorectal and prostate cancer. In addition to this, SNX9 is also required for Chlamydia trachomatis entry into cells and contributes to aberrant actin assemblies in a rare disease of phospho- inositide lipid metabolism, Lowe syndrome. It’s multifaceted nature is attributed to its structure. The SH3-PX-BAR domains of SNX9 are able to integrate inter- actions with phosphatidylinositol phosphates (PIPs) at membranes, and membrane curvature sensing to trigger actin polymerisation via the Arp2/3 complex. While membrane binding is key in in vitro purified reconstitutions of actin polymerisation, the lipid specificity and contribution of each membrane domain is under dispute and not well understood in vivo. Three models have been proposed for SNX9-membrane binding: (1) broad non- specific interactions with diverse phosphoinositides (PIPs), (2) the coincidence of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2) and phosphatidylinositol-(3)-pho- sphate (PI(3)P) each binding the BAR and PX-domains respectively or, (3) a particu- lar specificity for phosphatidylinositol-(3,4)-bisphosphate (PI(3,4)P2). To distinguish between these models, I used Surface Plasmon Resonance (SPR) and Bio-Layer Inter- ferometry (BLI) to determine the membrane specificity of SNX9. Both SPR and BLI studies confirm a SNX9 binding preference for PI(4,5)P2/PI(3)P at low SNX9 con- centrations whereas a more nuanced picture emerges at higher concentrations, where more SNX9 binds to PI(4,5)P2/PI(3)P liposomes. The affinity, however, is similar to the other compositions, suggesting SNX9 can assemble differently depending on PIPs present in the liposomes. Notably, SNX9 binding to PI(4,5)P2/PI(3)P…
abstract: Sorting nexin-9 (SNX9) is a SH3-PX-BAR domain-containing adaptor protein, func- tionally implicated in regulating actin polymerisation in clathrin mediated endocy- tosis and filopodia formation. Alterations in SNX9 expression correlate with several stages of breast cancer metastasis, and poor patient survival in colorectal and prostate cancer. In addition to this, SNX9 is also required for Chlamydia trachomatis entry into cells and contributes to aberrant actin assemblies in a rare disease of phospho- inositide lipid metabolism, Lowe syndrome. It’s multifaceted nature is attributed to its structure. The SH3-PX-BAR domains of SNX9 are able to integrate inter- actions with phosphatidylinositol phosphates (PIPs) at membranes, and membrane curvature sensing to trigger actin polymerisation via the Arp2/3 complex. While membrane binding is key in in vitro purified reconstitutions of actin polymerisation, the lipid specificity and contribution of each membrane domain is under dispute and not well understood in vivo. Three models have been proposed for SNX9-membrane binding: (1) broad non- specific interactions with diverse phosphoinositides (PIPs), (2) the coincidence of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2) and phosphatidylinositol-(3)-pho- sphate (PI(3)P) each binding the BAR and PX-domains respectively or, (3) a particu- lar specificity for phosphatidylinositol-(3,4)-bisphosphate (PI(3,4)P2). To distinguish between these models, I used Surface Plasmon Resonance (SPR) and Bio-Layer Inter- ferometry (BLI) to determine the membrane specificity of SNX9. Both SPR and BLI studies confirm a SNX9 binding preference for PI(4,5)P2/PI(3)P at low SNX9 con- centrations whereas a more nuanced picture emerges at higher concentrations, where more SNX9 binds to PI(4,5)P2/PI(3)P liposomes. The affinity, however, is similar to the other compositions, suggesting SNX9 can assemble differently depending on PIPs present in the liposomes. Notably, SNX9 binding to PI(4,5)P2/PI(3)P…
author: Vaishnav, Pankti
language: eng
keywords: SNX9, Phosphoinositides, PI(3,4)P2, PI(4,5)P2, Membrane curvature
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/75be3b93-3048-4d62-a9bd-a063509a0653/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-12-24
date modified: 2026-07-22T22:24:20Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.118312