Authors
Swayhoover, T., Weckerly, C., Hammond, G. R.
Abstract
PI(3,5)P2 is an endosomal lipid whose depletion is associated with a variety of pathologies such as neurodegenerative diseases. However, studying this lipid in physiological and disease models has been difficult due to the scarcity of the lipid and the lack of live-cell imaging tools. That is until recently, when a novel PI(3,5)P2 biosensor, SnxA, was characterized. In this work, we independently validated this promising biosensor by acutely depleting PI(3,5)P2 to show that SnxA depends on PI(3,5)P2 for membrane binding. We used a recruitable PIKfyve construct to demonstrate that ectopically generated PI(3,5)P2 at early endosomes and mitochondria was sufficient to recruit SnxA. Finally, we determined that SnxA shows higher affinity for PI(3,5)P2 when compared to other putative PI(3,5)P2 biosensors. Thus, we conclude that SnxA is a valid and sensitive PI(3,5)P2 biosensor that will facilitate real-time analysis of this understudied lipid.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 12 Nov 2025.
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