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ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes

ABSTRACT: Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. Recent work has raised the intriguing prospect that phase transitions in proteins and lipids can be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granules to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induces a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system serves as a potential regulatory mechanism in RNA trafficking and offers an important template to understand other examples across the cell whereby biomolecular condensates closely juxtapose organellar membranes.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Robin Antrobus

LAB HEAD: Dr Jonathon Nixon-Abell

PROVIDER: PXD060971 | Pride | 2025-02-19

REPOSITORIES: Pride

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