Biology subjects

Adicherla, H.

Publications and source records attributed to Adicherla, H..

3 recordsLinked to original sources

bioRxiv2024

Sporophyte Directed Gametogenesis via the Ubiquitin Proteasome System

Plants alternate between diploid sporophyte and haploid gametophyte generations. In mosses which retain features of ancestral land plants, the gametophyte is dominant and has an independent existence. However, in flowering plants the gametophyte has undergone evolutionary reduction to just a few cells enclosed within the sporophyte. The gametophyte is thought to retain genetic control of its development even after reduction. Here we demonstrate that male gametophyte development in Arabidopsis, long considered to be autonomous, is also under genetic control of the sporophyte via a repressive mechanism involving large-scale regulation of protein turnover. We identify an Arabidopsis gene SHUKR as an inhibitor of male gametogenesis. SHUKR is unrelated to proteins of known function and acts sporophytically in meiosis to control gametophyte development by negatively regulating expression of a large set of ubiquitination genes specific to post-meiotic gametogenesis. This control is late-emerging as SHUKR homologs are found only in eudicots. We show that SHUKR is rapidly evolving under positive selection suggesting that variation in control of protein turnover during male gametogenesis has played an important role in evolution within eudicots.

plant biology↗

bioRxiv2024

Inseparable/IER3IP1 are essential for cytokinesis in Drosophila neuroblast and human cells

To unveil the molecular players that maintain neural stem cell homeostasis, we conducted a genetic screen in Drosophila and isolated an uncharacterized gene that we named Inseparable (Insep). Insep is the Drosophila homologue of human IER3IP1, a gene associated with Microcephaly, Epilepsy, and Neonatal Diabetes Syndrome (MEDS-1). We show that Insep loss leads to early larval lethality with small brains and these phenotypes can be rescued by expressing IER3IP1 indicating that their biological function is conserved through evolution. The Insep deficient neuroblasts fail to complete cytokinesis and show excessive accumulation of Rab11 vesicles in the cytoplasm. Similarly, IER3IP1 depletion in human cells leads to cytokinesis failure and accumulation of Rab11 vesicles. Insep and IER3IP1 localize to Rab11 vesicles and interact with Rab11. The pathogenic mutations in IER3IP1 perturb its localization to Rab11 vesicles and interaction with Rab11. These results suggest that Insep and IER3IP1 work along with Rab11 and may regulate fusion of Rab11 vesicles to the advancing furrow during cytokinesis.

cell biology↗

bioRxiv2023

A host AAA-ATPase exhibits bacteriolytic activity for clearance of microbial infection

An array of host cytosol guarding factors impede bacterial proliferation and preserve cellular sterility. Amongst them, proteasomal degradation of ubiquitinated pathogens has emerged as a critical mechanism for ensuring cytosolic sanctity. We wondered how proteasomes, with their small size and inability to extract membrane-bound proteins, can eradicate pathogens. Here, we unveil a unique strategy, wherein VCP/p97, a host AAA-ATPase, eliminates pathogens by exerting mechanical force that physically unfolds and pulls out ubiquitinated proteins from bacterial membrane. Combining a single-molecule approach along with molecular dynamic simulation and in-vitro reconstitution, we demonstrate that protein extraction by p97 causes extensive membrane lysis and release of cytosolic contents from phylogenetically diverse microbes. Additionally, in an in-vivo mouse sepsis model, this segregase-dependent bactericidal effect of p97 abrogated microbial proliferation in host tissues. Overall, we discovered a distinct innate antimicrobial function of p97, that protects the host against lethal bacterial infections. One Sentence SummaryA host AAA-ATPase exhibits bacteriolytic activity.

microbiology↗