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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月21日

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  • Jonathon Nixon-Abell,
  • Francesco S. Ruggeri,
  • Seema Qamar,
  • Therese W. Herling,
  • Magdalena A. Czekalska,
  • Yi Shen,
  • Guozhen Wang,
  • Christopher King,
  • Michael S. Fernandopulle,
  • Tomas Sneideris,
  • Joseph L. Watson,
  • Visakh V. S. Pillai,
  • William Meadows,
  • James W. Henderson,
  • Joseph E. Chambers,
  • Jane L. Wagstaff,
  • Sioned H. Williams,
  • Helena Coyle,
  • Greta Šneiderienė,
  • Yuqian Lu,
  • Shuyuan Zhang,
  • Stefan J. Marciniak,
  • Stefan M. V. Freund,
  • Emmanuel Derivery,
  • Michael E. Ward,
  • Michele Vendruscolo,
  • Tuomas P. J. Knowles,
  • Peter St George-Hyslop

摘要

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.