Biology subjects

Nawrocka, A.

Publications and source records attributed to Nawrocka, A..

3 recordsLinked to original sources

bioRxiv2025

Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity

All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the C. elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. LPR-1 is apically secreted and colocalizes with LPR-3 in intracellular vesicles and lysosomes, but unlike LPR-3 it does not detectably incorporate into the aECM. Forward genetic screens for lpr-1 suppressors identified mutations in scav-2, which encodes a transmembrane protein of the CD36 scavenger receptor B family. Loss of scav-2 restored LPR-3 matrix localization and suppressed the lpr-1 tube shaping defect, as well as the tube-shaping defects of a subset of pre-cuticle mutants, but not lpr-3 mutants. A SCAV-2 fusion accumulated at apical surfaces of interfacial epithelial tubes, including the excretory duct and pore, and both tissue-specific suppression of lpr-1 matrix defects and tissue-specific rescue experiments support a local role for SCAV-2 within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of that tubes luminal aECM, possibly by acting as transporters of an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.

cell biology↗

bioRxiv2025

Sensory stimuli and cilium trafficking defects trigger the release of ciliary extracellular vesicles from multiple ciliary locations

The primary cilium is a signaling organelle that extends from many cell types to detect and relay extracellular signals. Beyond its signaling role, the cilium also produces cilia-derived extracellular vesicles (cEVs), although the mechanisms underlying their biogenesis and functions remain poorly understood. We characterized the cEV biogenesis in vivo using ciliated sensory neurons of C. elegans. In response to sensory cues, interruption of the intraflagellar transport (IFT) -a ciliary trafficking machinery carrying cargoes along the cilium-occurs together with ciliary membrane fission, resulting in the release of cEVs. Similarly, mutants disrupting IFT and ciliary receptor trafficking also enhance cEV production. To investigate how IFT influences the rate and location of cEV biogenesis, we selected a membrane marker that spans the entire length of the ciliary membrane independently of IFT. Single-molecule tracking demonstrates that the tetraspanin TSP-6 enters and diffuses within the cilia and does it independently of IFT. Lack of receptor retrieval or receptor entry in the cilium induces membrane budding from ciliary or periciliary membranes, respectively. Prior to fission, these membrane buds get enriched in TSP-6 as well as signaling receptors. Coupling receptor buildup with their export by cEVs provides a mechanism to preserve ciliary function and to modulate ciliary signaling. HIGHLIGHTS- The cone-shaped tetraspanin TSP-6 crosses the transition zone and moves by passive diffusion within the ciliary membrane, independently of IFT. - The production of ciliary EVs loaded with TSP-6 increases upon acute sensory stimulation or when IFT of ciliary membrane proteins is disrupted. - Depending on the nature of the perturbations, ciliary EVs remove excess material from the distal, proximal or periciliary segments of the cilia.

cell biology↗

bioRxiv2025

The RNA-binding protein RSRC2 promotes mitotic fidelity by interacting with the lncRNA C1QTNF1-AS1

Mitotic fidelity depends on proper chromosome alignment at the spindle equator, a process known as chromosome congression, driven by well-established protein networks. Whereas RNA-binding proteins and noncoding RNAs have been implicated in cell division, their interplay during this process remains unknown. Here, we discover that RSRC2, an arginine/serine-rich RNA-binding protein, plays an essential role in cell division by interacting with the long non-coding RNA C1QTNF1-AS1. The loss of either RSRC2 or C1QTNF1-AS1 results in defects in chromosome congression and mitotic progression. We show that RSRC2 interacts with distinct sets of proteins involved in splicing and centrosome biogenesis, contributing to the fidelity of cell division through two different mechanisms: one linked to the splicing of mitotic regulators and the other by localising to mitotic centrosomes for which the interaction with the C1QTNF1-AS1 RNA is required. Our study uncovers RSRC2 as a new regulator of cell division and illustrates how RNA-protein complexes promote error-free mitosis.

cell biology↗