Biology subjects

Knorr, R. L.

Publications and source records attributed to Knorr, R. L..

4 recordsLinked to original sources

bioRxiv2026

Shapes of condensate droplets containing filaments

The interactions of droplets and filaments can lead to mutual deformations and complex combined behavior. Such interactions also occur within the cell, where biomolecular condensates, distinct liquid phases often composed of proteins, have been observed to structure and affect the organization of the cytoskeleton. In particular, biomolecular condensates have been shown to undergo characteristic deformations when cytoskeletal filaments are fully embedded within them. However, a full understanding of the underlying physical mechanisms is still missing. Here, we combine experiments with coarse-grained molecular dynamics simulations and analytical models to uncover the physical mechanisms that define emerging shapes of droplets containing filaments. We find that the surface tension of the liquid phase and the bending energy of the filament(s) suffice to accurately capture emerging shapes if the length of the filament is small compared to the liquid volume. As the volume fraction of filament(s) increases, wetting effects become increasingly important, setting physical constraints within which surface and bending energies compete to define the droplet shapes. We find that mutual deformations of condensate and filament extend accessible shapes beyond classical stability considerations, leading to structuring and entrapment of contained filaments. Shape deformations may further affect ripening dynamics that favor certain geometries. Our findings provide a physical framework for a better understanding of the possible roles of biomolecular condensates in cytoskeletal organization.

biophysics↗

bioRxiv2025

Membrane protein condensates polymerize actin and form filopodia

Neuronal morphogenesis is guided by filopodia, dynamically generated plasma membrane protrusions filled with parallel actin filaments. However, how filopodial actin filaments are locally produced, organized, and maintained remains unclear. The transmembrane protein PLPPR3 induces filopodia in neurons and other cells. We find that the intracellular domain (ICD) of PLPPR3 forms liquid condensates, which exhibit strong co-partitioning of actin monomers. These condensates promote actin polymerization within the condensates at the expense of actin monomers in the environment, consistent with thermodynamic coupling of actin partitioning and polymerization, which we recapitulate in a modified polymerization kinetics model. This mechanism requires favorable actin partitioning into the condensate relative to the environment. Using crosslinking mass spectrometry, we identify a WH2-like actin-affinity domain within the PLPPR3 ICD. Deleting this domain lowers actin partitioning in vitro and decreases filopodia formation in vivo. Our findings establish a previously unrecognized mechanism for actin network remodeling, in which condensates act as actin sinks, locally boosting monomer concentrations and facilitating polymerization of actin filaments. One sentence summaryOur study uncovers PLPPR3 condensates to locally enrich actin monomers and promote actin polymerization, driving actin network remodeling and neuronal filopodia formation.

cell biology↗

bioRxiv2023

Autophagy adaptors mediate Parkin-dependent mitophagy by forming sheet-like liquid condensates

During PINK1 and Parkin-mediated mitophagy, autophagy adaptors are recruited to depolarized mitochondria to promote the selective degradation of mitochondria. Autophagy adaptors such as OPTN and NDP52 bridge mitochondria and autophagosomal membranes by binding to ubiquitinated mitochondrial proteins and autophagosomal ATG8 family proteins. Here, we demonstrate that OPTN and NDP52 form sheet-like phase-separated condensates with liquid-like properties on the surface of ubiquitinated mitochondria. The dynamic and liquid-like feature of OPTN condensates is important for mitophagy activity because reducing the liquidity of OPTN-ubiquitin condensates suppresses the recruitment of ATG9 vesicles and impairs mitophagy. Based on these results, we propose a dynamic liquid-like model of autophagy adaptors, in contrast to a stoichiometric model, to explain their interactions between autophagic membranes (i.e., ATG9 vesicles and isolation membranes) and mitochondrial membranes during Parkin-mediated mitophagy. This model underscores the importance of liquid-liquid phase separation in facilitating membrane- membrane contacts, likely through the generation of capillary forces.

cell biology↗

bioRxiv2019

Unrestrained ESCRT-III drives chromosome fragmentation and micronuclear catastrophe

The ESCRT-III membrane fission machinery1,2 restores nuclear envelope integrity during mitotic exit3,4 and interphase5,6. Whereas primary nuclei resealing takes minutes, micronuclear envelope ruptures appear irreversible and result in catastrophic collapse associated with chromosome fragmentation and rearrangements (chromothripsis), thought to be a major driving force in cancer development7-10. Despite its importance11-13, the mechanistic underpinnings of nuclear envelope sealing in primary nuclei and the defects observed in micronuclei remain largely unknown. Here we show that CHMP7, the nucleator of ESCRT-III filaments at the nuclear envelope3,14, and the inner nuclear membrane protein LEMD215 act as a compartmentalization sensor detecting the loss of nuclear integrity. In cells with intact nuclear envelope, CHMP7 is actively excluded from the nucleus to preclude its binding to LEMD2. Nuclear influx of CHMP7 results in stable association with LEMD2 at the inner nuclear membrane that licenses local polymerization of ESCRT-III. Tight control of nuclear CHMP7 levels is critical, as induction of nuclear CHMP7 mutants is sufficient to induce unrestrained growth of ESCRT-III foci at the nuclear envelope, causing dramatic membrane deformation, local DNA torsional stress, single-stranded DNA formation and fragmentation of the underlying chromosomes. At micronuclei, membrane rupture is not associated with repair despite timely recruitment of ESCRT-III. Instead, micronuclei inherently lack the capacity to restrict accumulation of CHMP7 and LEMD2. This drives unrestrained ESCRT-III recruitment, membrane deformation and DNA defects that strikingly resemble those at primary nuclei upon induction of nuclear CHMP7 mutants. Preventing ESCRT-III recruitment suppresses membrane deformation and DNA damage, without restoring nucleocytoplasmic compartmentalization. We propose that the ESCRT-III nuclear integrity surveillance machinery is a double-edged sword, as its exquisite sensitivity ensures rapid repair at primary nuclei while causing unrestrained polymerization at micronuclei, with catastrophic consequences for genome stability16-18.

cell biology↗