Biology subjects

Gross, E.

Publications and source records attributed to Gross, E..

3 recordsLinked to original sources

bioRxiv2022

The innovation of the symbiosome has enhanced the evolutionary stability of nitrogen fixation in legumes

O_LINitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2-fixing clade retained nodulation and diversified as stable nodulators while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades. C_LIO_LIWe characterize two nodule anatomy types across 128 species in 56 of the 150 genera of the legume subfamily Caesalpinioideae: 1) fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads and 2) symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes. C_LIO_LIUsing a robust phylogenomic tree based on 997 genes from 146 caesalpinioid genera, we show that losses of nodulation are more prevalent in lineages with FTs. C_LIO_LIWe propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through greater compartmentalisation of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical clade of legumes. C_LI

evolutionary biology↗

bioRxiv2020

A phospho-regulated ensemble signal motif of α-TAT1 drives dynamic microtubule acetylation

Spatiotemporally dynamic microtubule acetylation underlies diverse physiological events ranging from cell migration to intracellular trafficking, autophagy and viral infections. Despite its ubiquity, the molecular mechanisms that regulate the sole microtubule acetylating agent, -tubulin N-acetyltransferase 1 (-TAT1) remain obscure. Here we report that dynamic intracellular localization of -TAT1 unexpectedly determines the efficiency of microtubule acetylation. Specifically, we newly identified a conserved signal motif in the intrinsically disordered C-terminus of -TAT1, consisting of three competing regulatory elements - nuclear export, nuclear import and cytosolic retention. Their balance is tuned via phosphorylation by serine-threonine kinases including CDK1 and CK2. While the un-phosphorylated form resides both in the cytosol and nucleus, the phosphorylated form binds to specific 14-3-3 adapters and accumulates in the cytosol for maximal substrate access. Cytosolic localization of -TAT1 predominantly mediates microtubule acetylation, cell proliferation and DNA damage response. In contrast to other molecules with a similar phospho-regulated signal motif including transcription factors, -TAT1 uniquely uses the nucleus as a hideout. As amino acid mutations to the motif have been reported in cancer patients, the present mechanism of subcellular -TAT1 localization may help uncover a spatiotemporal code of microtubule acetylation in normal and aberrant cell functions.

cell biology↗

bioRxiv2020

A tyrosine kinase protein interaction map reveals targetable EGFR network oncogenesis in lung cancer

SUMMARYSignaling networks balance the activities of many physically interacting proteins and perturbations to this network influence downstream signaling, potentially leading to oncogenic states. Using affinity purification-mass spectrometry we defined this network for all 90 human tyrosine kinases revealing 1,463 mostly novel interactions between these key cancer proteins and diverse molecular complexes. Modulation of interactor levels altered growth phenotypes associated with corresponding tyrosine kinase partners suggesting that tumors may alter the stoichiometries of interactors to maximize oncogenic signaling. We show that the levels of EGFR interactors delineates this form of network oncogenesis in 19% of EGFR wild-type lung cancer patients which were mostly otherwise oncogene negative, predicting sensitivity to EGFR inhibitors in vitro and in vivo. EGFR network oncogenesis occurs through mechanistically distinct network alleles often in cooperation with weak oncogenes in the MAPK pathway. Network oncogenesis may be a common and targetable convergent mechanism of oncogenic pathway activation in cancer.HIGHLIGHTSA human tyrosine kinome protein interaction map reveals novel physical and functional associations.Dependence on oncogenic tyrosine kinases is modulated through perturbation of their interactors.EGFR network oncogenesis in up to 19% of EGFR wild-type lung cancers is targetable.EGFR network oncogenesis cooperates with weak oncogenes in the MAPK pathway.Competing Interest StatementS.L.W. is an employee of Pfizer. D.C., I.S., E.M., are employees of Champions oncology. S.B. has received funding from Clovis Oncology, Pfizer, Revolution Medicines and Ideaya Biosciences.View Full Text

cancer biology↗