Biology subjects

Conacci-Sorrell, M.

Publications and source records attributed to Conacci-Sorrell, M..

3 recordsLinked to original sources

bioRxiv2024

Anchorage-independent cell proliferation promoted by fascin's F-actin bundling

The actin filament (F-actin) bundling protein fascin-1 is highly enriched in many metastatic cancers. Fascins contribution to metastasis have been ascribed to its enhancement of cell migration and invasion. However, mouse genetic studies clearly point to functions also in tumorigenesis, yet without mechanistic underpinnings. Here, we show that fascin expression promotes the formation of a non-canonical signaling complex that enables anchorage-independent proliferation. This complex shares similarities to focal adhesions and we refer to them as pseudo-adhesion signaling scaffolds (PASS). PASS are enriched with tyrosine phosphorylated proteins and require fascins F-actin-bundling activity for its assembly. PASS serve as hubs for the Rac1/PAK/JNK proliferation signaling axis, driven by PASS-associated Rac-specific GEFs. Experimental disruption of either fascin or RacGEF function abrogates sustained proliferation of aggressive cancers in vitro and in vivo. These results add a new molecular element to the growing arsenal of metabolic and oncogenic signaling programs regulated by the cytoskeleton architecture.

cell biology↗

bioRxiv2022

Increasing the Field-of-View in Oblique Plane Microscopy via optical tiling

Fast volumetric imaging of large fluorescent samples with high-resolution is required for many biological applications. Oblique plane microscopy (OPM) provides high spatiotemporal resolution, but the field of view is typically limited by its optical train and the pixel number of the camera. Mechanically scanning the sample or decreasing the overall magnification of the imaging system can partially address this challenge, albeit by reducing the volumetric imaging speed or spatial sampling, respectively. In this Letter, we introduce a novel dual-axis scan unit for OPM that enables rapid and high-resolution volumetric imaging throughout a volume of 800 x 500 x 200 microns. This enables imaging of model organisms, such as zebrafish embryos, with subcellular resolution. Furthermore, we combined this microscope with a real-time and multi-perspective projection imaging technique to increase the volumetric interrogation rate to more than 10 Hz.

bioengineering↗

bioRxiv2022

ZNF692 organizes a hub for ribosome maturation enhancing translation in rapidly proliferating cells

Rapidly proliferating cells produce more ribosomes to translate sufficient proteins for cell growth. One of the first and rate limiting steps in translation initiation is the interaction of the small ribosomal subunit with mRNAs. Therefore, effective small ribosomal subunit biogenesis is critical for translation initiation efficiency. Here we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small 40S ribosome. ZNF692 forms a complex with rRNA, the 90S processome and the nucleolar exosome in the granular component of the nucleolus creating a hub specialized in the final steps of 18S processing and small ribosomal subunit maturation. Cancer cells are more reliant on ZNF692 for increased translation than normal cells. We propose that MYC increases translation efficiency by promoting the expression of ZNF692, adjusting the translation rate to the increase in mRNA transcription induced by MYC.

molecular biology↗