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Antkowiak, A.

Publications and source records attributed to Antkowiak, A..

3 recordsLinked to original sources

Temporal tuning of actin nucleation by the repurposed DNA repair complex RAD51/fignl1 encodes distinct axon guidance decisions

Axon guidance is essential for neural circuit assembly and function. While much of the repertoire of guidance cues and receptors is known, its limited diversity cannot fully explain the remarkable complexity of the brain connectome. How temporally ordered, context-dependent intrinsic programs shape the diversity of axonal responses to guidance signals remains poorly understood. We reveal how non-canonical Wnt5a signalling repurposes the DNA repair complex RAD51/fignl1 as a downstream integrator to control retinal ganglion cell axon decision-making at the midline. We demonstrate that differential RAD51/fignl1 expression and interaction dynamics between ipsilateral and contralateral axons tunes the magnitude and temporal dynamics of F-actin nucleation, thereby encoding their trajectory choice. Our findings establish temporal control of cytoskeletal dynamics as a key determinant of axon decision-making and thereby a fundamental layer of circuit wiring. They provide a potential mechanistic framework linking mutations in the DNA repair gene RAD51 to neurodevelopmental disorders with midline guidance defects.

neuroscience↗

Specialization of actin isoforms derived from the loss of key interactions with regulatory factors

A paradox of eukaryotic cells is that while some species assemble a complex actin cytoskeleton from a single ortholog, other species utilize a greater diversity of actin isoforms. The physiological consequences of using different actin isoforms, and the molecular mechanisms by which highly conserved actin isoforms are segregated into distinct networks, are poorly known. Here, we sought to understand how a simple biological system, composed of a unique actin and a limited set of actin-binding proteins, reacts to a switch to heterologous actin expression. Using yeast as a model system and biomimetic assays, we show that such perturbation causes drastic reorganization of the actin cytoskeleton. Our results indicate that defective interaction of a heterologous actin for important regulators of actin assembly limits certain actin assembly pathways while reinforcing others. Expression of two heterologous actin variants, each specialized in assembling a different network, rescues cytoskeletal organization and confers resistance to external perturbation. Hence, while species using a unique actin have homeostatic actin networks, actin assembly pathways in species using several actin isoforms may act more independently.

cell biology↗

Adhesion of dry and wet cribellate capture silk

We demonstrate the impressive adhesive qualities of Uloborid spider orbweb capture when dry, which are lost when the nano-filament threads are wetted. A force sensor with a 50 nN-1mN detection sensitively allowed us to measure quantitatively the stress-strain characteristics of native silk threads in both the original dry state and after wetting by controlled application of water mist with droplet sizes ranging between 3 and 5 m and densities ranging between 104 and 105 per mm3. Stress forces of between 1 and 5 N/m2 in the native, dry multifilament thread puffs were reduced to between 0.1 and 0.5 N/m2 in the wetted collapsed state, with strain displacements reducing from between 2 and 5 mm in the dry to 0.10-0.12mm in the wetted states. We conclude that wetting cribellate threads reduce their van der Waals adhesion with implications on the threads adhesive strength under tension. This should be considered when discussing the evolutionary transitions of capture silks from the ancestral dry-state nanofilaments of the cribellate spider taxa to the wet-state glue droplets of the ecribellate taxa.

zoology↗