Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli

Abstract

A supervised machine learning algorithm, which is qualified for image classification and analyzing similarities, is based on multiple discriminative morphological features that are automatically assembled during the learning processes. The algorithm is suitable for population-based analysis of images of biological materials that are generally complex and heterogeneous. Here we used the algorithm wndchrm to quantify the effects on nucleolar morphology of the loss of the components of nuclear envelope in a human mammary epithelial cell line. The linker of nucleoskeleton and cytoskeleton (LINC) complex, an assembly of nuclear envelope proteins comprising mainly members of the SUN and nesprin families, connects the nuclear lamina and cytoskeletal filaments. The components of the LINC complex are markedly deficient in breast cancer tissues. We found that a reduction in the levels of SUN1, SUN2, and lamin A/C led to significant changes in morphologies that were computationally classified using wndchrm with approximately 100% accuracy. In particular, depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis. Further, wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. Our unbiased morphological quantitation strategies using wndchrm revealed an unexpected link between the components of the LINC complex and the morphologies of nucleoli that serves as an indicator of the malignant phenotype of breast cancer cells.

A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair

“…Indeed, the LINC complex plays roles in mobilization of damaged telomeres and IR-induced DSBs in mouse cells (Lottersberger et al 2015) and also contributes to DSBs clustering in human nuclei (Aymard et al 2017). Interestingly, SUN1, a subunit of the LINC complex localizing to the NE, was also reported recently to be present in nucleoli (Matsumoto et al 2016;Moujaber et al 2017). In agreement, we could indeed confirm that SUN1 forms patches close to RNA Pol I (Supplemental Fig.…”

OPENER Is a Nuclear Envelope and Mitochondria Localized Protein Required for Cell Cycle Progression in Arabidopsis

“…Previous studies have suggested that LINC complexes are involved in regulating nuclear movement, nuclear positioning, nuclear morphology, and chromatin-nuclear envelope interactions (Starr and Fridolfsson, 2010;Tapley and Starr, 2013). Animal SUN proteins are known to be involved in various processes including maintaining nuclear and nucleolar morphology, meiosis, mitosis, DNA damage responses, and mRNA export (Lei et al, 2012;Turgay et al, 2014;Li and Noegel, 2015;Lawrence et al, 2016;Matsumoto et al, 2016).…”

Computational analysis of morphological and molecular features in gastric cancer tissues

“…Cross‐validation tests were automatically repeated 20 times to validate classification performance. As described previously, dendrograms and morphological distances were identified using the Fitch‐Margoliash method and calculating Euclidian distances (d = √Σ(A−B) 2 ), respectively. Fisher scores were computed from 4,059 (24‐bit color) or 2919 (8‐bit gray) image features from the following: Chebyshev‐Fourier transform (ChFT), Chebyshev Statistics (Ch), Combined First Four Moments (Cf4M), Fractal Statistics (Fra), Haralick Texture (Har), Multiscale Histogram (MSH), Radon (Rad), and Zernike (Zer), and the others (others) .…”