TY - JOUR
T1 - ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
AU - Nixon-Abell, Jonathon
AU - Ruggeri, Francesco S.
AU - Qamar, Seema
AU - Herling, Therese W.
AU - Czekalska, Magdalena A.
AU - Shen, Yi
AU - Wang, Guozhen
AU - King, Christopher
AU - Fernandopulle, Michael S.
AU - Sneideris, Tomas
AU - Watson, Joseph L.
AU - Pillai, Visakh V.S.
AU - Meadows, William
AU - Henderson, James W.
AU - Chambers, Joseph E.
AU - Wagstaff, Jane L.
AU - Williams, Sioned H.
AU - Coyle, Helena
AU - Šneiderienė, Greta
AU - Lu, Yuqian
AU - Zhang, Shuyuan
AU - Marciniak, Stefan J.
AU - Freund, Stefan M.V.
AU - Derivery, Emmanuel
AU - Ward, Michael E.
AU - Vendruscolo, Michele
AU - Knowles, Tuomas P.J.
AU - St George-Hyslop, Peter
PY - 2025/3/21
Y1 - 2025/3/21
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-025-58142-5
DO - 10.1038/s41467-025-58142-5
M3 - Article
AN - SCOPUS:105000484872
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
M1 - 2814
ER -