Biology subjects

Zezula, N.

Publications and source records attributed to Zezula, N..

2 recordsLinked to original sources

bioRxiv2025

Proximity interactomics identifies RAI14, EPHA2 and PHACTR4 as essential components of Wnt/planar cell polarity pathway in vertebrates

Wnt/planar cell polarity (Wnt/PCP) pathway is an evolutionarily conserved signaling cascade playing an inevitable role in cell biology. Deregulation of Wnt/PCP leads to severe developmental defects or cancer progression. Here, we applied proximity-dependent biotinylation (BioID) to capture the intracellular interactome of key Wnt/PCP components: transmembrane ROR1, ROR2 and VANGL2, and cytoplasmic DVL3 and PRICKLE1. Mapping of individual preys across the baits and subcellular compartments identified a group of 30 proteins that we tested by loss-of-function in zebrafish. Among those rai14, epha2 and phactr4 were essential for several Wnt/PCP-dependent processes such as zebrafish convergent extension, orientation of lateral organ cells, or migration of melanoma cells. Mechanistically, RAI14, EPHA2 and PHACTR4 connect the receptor complex to effector actomyosin. In summary, this study identified novel essential components of vertebrate WNT/PCP pathway and provides a detailed characterization of PCP complex composition that can serve as comprehensive resource for further analysis of Wnt/PCP function.

cell biology↗

bioRxiv2020

Lyn controls chemotaxis and motility of CLL cells via phosphorylation of ROR1.

Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are malignancies characterized by the dependence on B-cell receptor (BCR) signaling and by the high expression of the cell surface receptor ROR1. Both, BCR and ROR1 are therapeutic targets in these diseases and the understanding of their mutual cross talk is thus of direct therapeutic relevance. In this study we analyzed the role of Lyn, a kinase from the Src family, as a mediator of the BCR-ROR1 crosstalk. We confirm the functional interaction between Lyn and ROR1 and demonstrate that Lyn kinase efficiently phosphorylates ROR1 in its kinase domain and aids the recruitment of an E3 ligase c-CBL. The absence of Lyn in Lyn KO Maver-1 cells produced by CRISPR-Cas9 resulted in the increased ROR1 cell surface levels and deregulated migratory properties. Similar correlations between ROR1 surface dynamics, levels of active Lyn and chemotactic properties were confirmed in primary CLL samples. Our data establish Lyn-mediated phosphorylation of ROR1 as a point of crosstalk between BCR and ROR1 signaling pathways.

cancer biology↗