Biology subjects

Knyazeva, A.

Publications and source records attributed to Knyazeva, A..

3 recordsLinked to original sources

bioRxiv2024

ESCRT recruitment to damaged lysosomes is dependent on the ATG8 E3-like ligases

The endosomal sorting complex required for transport (ESCRT) machinery plays an essential role in the sealing of endolysosomal membranes damaged by pathogenic, chemical or physical stress. How membrane damage is sensed by the cell and then translated into the recruitment of the ESCRT machinery is largely unknown. Here, we show that damage-dependent translocation of the autophagy ATG8 E3-like ligases to lysosomal membranes acts as the catalyst for ESCRT recruitment. Leakage of protons or calcium from perforated lysosomes induces V-ATPase-dependent or sphingomyelin-dependent recruitment of the ATG16L1-ATG5-ATG12 or TECPR1-ATG5-ATG12 E3-like complex, respectively. We show that E3-like complex-dependent recruitment of the ATG5-ATG12 conjugate to the damaged membrane is an essential prerequisite to ESCRT recruitment. At the damaged membrane ATG5-ATG12 plays both a conjugation-dependent and conjugation-independent role in stabilizing the calcium sensor, ALG-2, and recruiting the downstream repair complex. For the former scenario, we demonstrate that LC3B binds directly to ALG-2 in a Ca2+ dependent manner. This places the ATG8 E3-like ligases in the role of damage sensors for ESCRT- mediated membrane repair. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/591897v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@11e4d07org.highwire.dtl.DTLVardef@534095org.highwire.dtl.DTLVardef@1b535f7org.highwire.dtl.DTLVardef@1ea0ac7_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Chemogenetic inhibition of IST1-CHMP1B interaction impairs endosomal recycling and promotes unconventional LC3 lipidation at stalled endosomes

The Endosomal Sorting Complex Required for Transport (ESCRT) machinery constitutes a multisubunit protein complex that plays an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, encompassing cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair and autophagy. Given the versatile functionality of ESCRTs and the intricate organizational structure of the ESCRT complex, the targeted modulation of distinct ESCRT-mediated membrane deformations for functional dissection poses a considerable challenge. This study presents a pseudo-natural product targeting IST1-CHMP1B within the ESCRT-III complex. This compound specifically disrupts the interaction between IST1 and CHMP1B, thereby inhibiting the formation of IST1-CHMP1B copolymers essential for normal-topology membrane scission events. While the compound has no impact on cytokinesis, MVB sorting and exosome biogenesis, it rapidly hinders transferrin receptor (TfR) recycling in cells, resulting in the accumulation of transferrin in perinuclear endosomal recycling tubules. Stalled recycling endosomes acquire unconventional LC3 lipidation, establishing a link between non-canonical LC3 lipidation and endosomal recycling.

cell biology↗

bioRxiv2017

Coat color allele and mtDNA haplotype distributions in Russian cat populations: a citizen-science research

This work has started as a project for the summer school in molecular and theoretical biology. Efficient teaching and learning modern methods of molecular biology and population genetics in a two-week study course for high school students needs an attractive subject. We chose phylogeography of the domestic cat as the subject of our project because 1) everybody likes cats; 2) cats are polymorphic for several coat color mutations, which can be easily detected by street survey or in the photographs; 3) samples for DNA extraction are easy to collect without posing ethical and biosafety problems; 4) rich background information of geographical distribution of coat color alleles and variation in mtDNA is available; 5) phylogeography of cat population in Russia is poorly studied and therefore new data collected in this large territory may shed a light on the global cat distribution and on the origin of the fancy breeds.\n\nDuring the project students studied coat color and mitotype distribution across Russian random bred cats. The basics of field (observations of natural cat populations, hair collection), formal (inheritance of coat colors), mathematical population (allele frequency distributions and their comparisons, building phylogenetic trees, multidimensional scaling), and molecular (DNA extraction and amplification, quality control of DNA sequencing data) genetics were covered.\n\nWe scored coat color phenotypes in 1182 cats and sequenced mtDNA control region from hair samples of 38 cats from 18 geographical sites. Analysis of coat color alleles frequencies and mitotype distribution confirmed relative homogeneity of gene pools of Russian cat populations, indicating their recent origin. We found several unique mitotypes and demonstrated that OL1 mitotype, previously found only in Siberian fancy breed, was present in random bred cats from several Russian cities. This contributes to the discussion on the origin of the Siberian breed of cats, and supports the view that Siberians is a recent breed created in the 1980s by breeding of selected representatives of the random bred population.

genetics↗