Biology subjects

Harizanova, J.

Publications and source records attributed to Harizanova, J..

3 recordsLinked to original sources

bioRxiv2023

The actin cytoskeleton plays multiple roles in structural color formation in butterfly wing scales

Vivid structural colors in butterflies are caused by photonic nanostructures scattering light. Structural colors evolved for numerous biological signaling functions and have technological applications. Optically, such structures are well understood, however their development in vivo remains obscure. We show that actin is intimately involved in structural color formation in the butterfly Heliconius sara. Using comparisons between iridescent (structurally colored) and non-iridescent scales in adult and developing H. sara, we show that iridescent scales have more densely packed actin bundles leading to an increased density of reflective ridges. Super-resolution microscopy revealed that actin is repeatedly re-arranged in later development, when optical nanostructures are forming. Furthermore, actin perturbation experiments at these later developmental stages resulted in near total loss of structural color. Overall, this shows that actin plays vital templating roles during structural color formation in butterfly scales, with mechanisms potentially universal across lepidoptera. TeaserThe actin cytoskeleton is essential for templating the optical nanostructures responsible for structural color production in butterfly scales. Actin templates the reflective ridges on butterfly scales and is directly involved in forming the color-producing nanostructures within these

developmental biology↗

bioRxiv2018

PDEδ inhibition impedes the proliferation and survival of human colorectal cancer cell lines harboring oncogenic KRas

Novelty and ImpactThe undruggable KRas is a prevalent oncogene in CRC with poor prognosis. In hPDAC cells pharmacological targeting of PDE{delta} affects oncogenic KRas signaling, but it remained unclear whether this approach is transferable to other cancer cells. Here, we show that genetic and pharmacologic PDE{delta} inhibition also impedes the proliferation of oncogenic, but not wild-type KRas bearing CRC cells indicating that PDE{delta} inhibition is a specific tool for targeting growth of oncogenic KRas bearing CRC.\n\nAbstractRas proteins, most notably KRas, are prevalent oncogenes in human cancer. Plasma membrane localization and thereby signaling of KRas is regulated by the prenyl-binding protein PDE{delta}. Recently, we have reported the specific anti-proliferative effects of PDE{delta} inhibition in KRas-dependent human pancreatic ductal adenocarcinoma cell lines. Here, we investigated the proliferative dependence on the solubilizing activity of PDE{delta} of human colorectal cancer (CRC) cell lines with or without oncogenic KRas mutations. Our results show that genetic and pharmacologic interference with PDE{delta} specifically inhibits proliferation and survival of CRC cell lines harboring oncogenic KRas mutations whereas isogenic cell lines in which the KRas oncogene has been removed, or cell lines with oncogenic BRaf mutations or EGFR overexpression are not dependent on PDE{delta}. Pharmacological PDE{delta} inhibition is therefore a possible new avenue to target oncogenic KRas bearing CRC.

cell biology↗

bioRxiv2017

Assay to visualize specific protein oxidation reveals spatio-temporal regulation of SHP2

Reactive oxygen species (ROS) are produced transiently in response to cell stimuli, and function as second messengers that oxidize target proteins. Protein-tyrosine phosphatases (PTPs) are important ROS targets, whose oxidation results in rapid, reversible, catalytic inactivation. Despite increasing evidence for the importance of PTP oxidation in signal transduction, the cell biological details of ROS-catalyzed PTP inactivation have remained largely unclear, due to our inability to visualize PTP oxidation in cells. By combining proximity ligation assay (PLA) with chemical labeling of cysteine residues in the sulfenic acid state, we visualize oxidized Src homology 2 domain-containing protein-tyrosine phosphatase 2 (SHP2). We find that platelet-derived growth factor (PDGF) evokes transient oxidation on or close to RAB5+/EEA1-endosomes. SHP2 oxidation requires NADPH oxidases (NOXs), and oxidized SHP2 co-localizes with PDGF receptor and NOX1/4. Our data demonstrate spatially and temporally limited protein oxidation within cells, and suggest that PDGF-dependent \"redoxosomes,\" contribute to proper signal transduction.

cell biology↗