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| Format: | Recurso digital |
| Language: | English |
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2026
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| Online Access: | https://doi.org/10.5281/zenodo.19938527 |
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| _version_ | 1866901371513470976 |
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| author | Low, Jia Hua (Jensen) |
| author_facet | Low, Jia Hua (Jensen) |
| contents | <p class="MsoNormal">HSPA1A is a molecular chaperone that regulates cellular homeostasis under stress and is frequently upregulated in cancer cells. In addition to its cytosolic functions, HSPA1A localizes to the plasma membrane (PM) in stressed and tumor cells, where it is associated with increased cell survival and therapeutic resistance. Despite its importance, the mechanisms underlying HSPA1A translocation to the PM remain poorly understood. Based on previous findings that HSPA1A associates with specific lipids, I hypothesized that its PM localization is mediated through a lipid-dependent vesicular trafficking mechanism. Confocal imaging showed that HSPA1A redistributes across endosomal compartments following heat shock, with increased association with recycling and lysosomal pathways and dynamic localization to phosphoinositide-enriched membranes. Pharmacological perturbation of lipid composition modestly reduced HSPA1A PM localization. Inhibition of ER-Golgi transport had no effect, whereas disruption of endosomal and lysosomal pathways resulted in small but significant reductions, suggesting that multiple vesicular routes contribute to HSPA1A trafficking. Modulation of lysosomal lipid composition and phosphoinositide regulation further demonstrated that BMP levels and Sac1 activity influence HSPA1A PM localization. Together, these findings support a model in which HSPA1A is trafficked to the PM through lipid-dependent vesicular pathways regulated by lipid composition and compartment-specific lipid dynamics.</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19938527 |
| institution | Zenodo |
| language | eng |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | VESICULAR TRAFFICKING OF HSPA1A TO THE PLASMA MEMBRANE OF HEAT-SHOCKED CELLS Low, Jia Hua (Jensen) heat shock response HSPA1A trafficking lipid-protein interactions endo-lysosomal pathway vesicular transport phosphoinositides <p class="MsoNormal">HSPA1A is a molecular chaperone that regulates cellular homeostasis under stress and is frequently upregulated in cancer cells. In addition to its cytosolic functions, HSPA1A localizes to the plasma membrane (PM) in stressed and tumor cells, where it is associated with increased cell survival and therapeutic resistance. Despite its importance, the mechanisms underlying HSPA1A translocation to the PM remain poorly understood. Based on previous findings that HSPA1A associates with specific lipids, I hypothesized that its PM localization is mediated through a lipid-dependent vesicular trafficking mechanism. Confocal imaging showed that HSPA1A redistributes across endosomal compartments following heat shock, with increased association with recycling and lysosomal pathways and dynamic localization to phosphoinositide-enriched membranes. Pharmacological perturbation of lipid composition modestly reduced HSPA1A PM localization. Inhibition of ER-Golgi transport had no effect, whereas disruption of endosomal and lysosomal pathways resulted in small but significant reductions, suggesting that multiple vesicular routes contribute to HSPA1A trafficking. Modulation of lysosomal lipid composition and phosphoinositide regulation further demonstrated that BMP levels and Sac1 activity influence HSPA1A PM localization. Together, these findings support a model in which HSPA1A is trafficked to the PM through lipid-dependent vesicular pathways regulated by lipid composition and compartment-specific lipid dynamics.</p> |
| title | VESICULAR TRAFFICKING OF HSPA1A TO THE PLASMA MEMBRANE OF HEAT-SHOCKED CELLS |
| topic | heat shock response HSPA1A trafficking lipid-protein interactions endo-lysosomal pathway vesicular transport phosphoinositides |
| url | https://doi.org/10.5281/zenodo.19938527 |